Diabetes: Type 1

Description

Alternative Names

Treatment

Insulin is essential for strict control of blood glucose levels in type 1 diabetes, which is now established as the best way to prevent major complications in type 1 diabetes, including in the kidney, eyes, nerve pathways, and blood vessels. Although its effects on heart disease and stroke are less clear, evidence suggests intensive control will also have benefits for these major problems. Intensive insulin treatment in early diabetes may even help preserve any residual insulin secretion for at least two years.

There are, however, some significant problems with intensive insulin therapy:

• There is a higher risk for hypoglycemia, a possibly dangerous drop in blood glucose levels.
• Many patients experience significant weight gain from insulin administration, which may have adverse effects on blood pressure and cholesterol levels. It is important to manage cardiovascular risk factors that might develop as a result of intensive treatment.

A diet plan that compensates for insulin administration and supplies healthy foods is extremely important. [For detailed information, see 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. In one major study, even when levels were 40% higher than nondiabetic 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 a number of variations of insulin delivery for accomplishing them:

• Basal insulin administration. The basal component of the treatment attempts to provide a steady amount of background insulin throughout the day. Basal insulin levels maintain regular blood glucose needs. Insulin glargine now offers the most consistent insulin activity level, but other intermediate- and long-acting forms may be beneficial when administered twice a day. Short-acting insulin delivered continuously using a pump is proving to a very good way to provide basal rates of insulin.
• Mealtime insulin administration. Meals require a boost (a bolus) of insulin to regulate the sudden rise in glucose levels after a meal.

In achieving insulin control the patient must also take other steps:

• The patient should perform four or more blood glucose tests during the day.
• Patients should coordinate insulin administration with calorie intake. In general, they should eat three meals each day at regular intervals. Snacks are often required.
• Insulin requirements vary depending on many non-nutritional situations during the day, including exercise and sleep. People are at enhanced risk for low blood sugar during exercise. Some patients experience a sudden rise in blood glucose levels in the morning--the so-called "dawn phenomenon."
• The patient must also maintain a good diet plan and should visit the health care team of doctors, nurses, and dietitians once a month.

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:

• The duration of insulin action. Insulin is available in several forms, including standard-, intermediate-, long-, and rapid-acting.
• Amount and type of food eaten. Ingestion of food makes the blood glucose level rise. Alcohol lowers levels.
• The person's level of physical activity. Exercise lowers glucose levels.

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. Regular insulin may be administered before a meal and may be better for high-fat meals.

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, such as insulin glargine (Lantus), are released slowly. Insulin glargine 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. Detemir, another basal insulin form, is being investigated and might pose a lower risk for weight gain than others. Ultralente insulin peaks at 10 hours and lasts up to 20 hours but varies greatly in activity from day to day.

Fast-Acting Insulin. Insulin lispro (Humalog) and insulin aspart (Novo Rapid, Novolog) lower blood sugar very quickly and are short acting (lasting about four hours). This short action reduces the risk for hypoglycemic events after eating (postprandial hypoglycemia). Optimal timing for administering this insulin is about fifteen minutes before a meal, but it can be also taken immediately after a meal (but within 30 minutes). Fast-acting insulins may be especially useful for meals with high carbohydrates. In one study, lispro helped reduce the risk for nighttime hypoglycemia in children. Evidence suggests that short-acting insulin may improve quality of life compared to regular insulin. There is some concern that short-acting forms may cause birth defects if pregnant women take them. More research is needed to define the risk.

Combinations. Regimens generally include combinations of short and longer-acting insulins to help match the natural cycle. For example, one approach in patients who are intensively controlling their glucose levels uses three injections of insulin, which includes a mixture of regular insulin and NPH at dinner. Another approach uses four-injections, including a separate short-acting form at dinner and NPH at bedtime, which may pose a lower risk for nighttime hypoglycemia than the three-injection regimen.

Alternative Methods for Delivering Insulin

Insulin Pumps. The use of the insulin pump is proving to control blood glucose control and improve quality of life with fewer hypoglycemic episodes than multiple injections. The pumps correct for the so-called dawn phenomenon and allow quick reductions for specific situations, such as exercise. Many brands are available (e.g., IR-1000, Cozmo, H-Tron Plus, D-Tron Plus, Minimed Paradigm, Dana Diabecare II.)

The typical pump is about the size of a pack of beeper and has a digital display. Some are worn externally and are programmed to deliver insulin through a catheter in the skin or the abdomen. They generally use rapid-acting insulin, which is the most predictable type. They work by administering a small amount of insulin continuously (the basal rate) and a higher dose (a bolus dose) when food is eaten.

At this time, adults and adolescents use the pumps, but they are proving to be helpful for children with diabetes, even very young children.

The catheter at the end of the insulin pump is inserted through a needle into the abdominal fat of a person with diabetes. Dosage instructions are entered into the pump's small computer and the appropriate amount of insulin is then injected into the body in a calculated, controlled manner.

Learning to use the pump can be complicated, although over time most patients find they are fairly easy to use. To achieve good control, patients and parents of children must undergo some training. The user and physician must determine the amount of insulin used-- it is not automatically calculated. This requires an initial learning period, including understanding insulin needs over the course of the day and in different situations and knowledge of carbohydrate counting. Frequent blood testing is very important, particularly during the training period.

They are more expensive than insulin shots and occasionally have some complications, such as blockage in the device or skin irritation at the infusion site. In spite of early reports of a higher risk for ketoacidosis with the pumps, more recent studies have found no higher risk.

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). Inhalants cannot completely replace injections altogether but may be useful before meals. They also might be useful for people with type 2 diabetes or in emergency situations when a rapid insulin boost is needed. The spray may have better effects on cholesterol levels than the inhaled form does. In fact, some studies report higher cholesterol levels with the inhaled insulin. The reasons for this are unclear.

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, in patients with type 1 diabetes. Postprandial hyperglycemia is now believed to be a significant long-term threat to the body.

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. It, therefore, prevents the surge in blood sugar that typically occurs after meals. It is proving to help control glucose after meals in combination with insulin, regardless of whether it is regular or fast-acting insulin or delivered with a pump. It does not appear to add any greater risk for weight gain or hypoglycemia. It is being considered for approval for both type 1 and type 2 insulin-dependent diabetes. No serious adverse effects have been reported to date. There is some concern that the delay in stomach emptying may pose problems for diabetics who are already experiencing this as a complication of neuropathy.