How is diabetes treated?

How is diabetes treated?

Diabetes At A Glance
• Diabetes is a chronic condition associated with abnormally high levels of sugar (glucose) in the blood.
• Insulin produced by the pancreas lowers blood glucose.
• Absence or insufficient production of insulin causes diabetes.
• The two types of diabetes are referred to as type 1 (insulin dependent) and type 2 (non-insulin dependent).
• Symptoms of diabetes include increased urine output, thirst and hunger as well as fatigue.
• Diabetes is diagnosed by blood sugar (glucose) testing.
• The major complications of diabetes are both acute and chronic.
o Acutely: dangerously elevated blood sugar, abnormally low blood sugar due to diabetes medications may occur.
o Chronically: disease of the blood vessels (both small and large) which can damage the eye, kidneys, nerves, and heart may occur
• Diabetes treatment depends on the type and severity of the diabetes. Type 1 diabetes is treated with insulin, exercise, and a diabetic diet. Type 2 diabetes is first treated with weight reduction, a diabetic diet, and exercise. When these measures fail to control the elevated blood sugars, oral medications are used. If oral medications are still insufficient, insulin medications are considered.



Last Editorial Review: 12/5/2006

Diabetes Treatment
Medical Author: Ruchi Mathur, MD
Medical Editor: William C. Shiel, Jr., MD, FACP, FACR and Jay W. Marks, MD
• How is diabetes treated?
• Medications for type 2 diabetes
• Sulfonylureas
• Meglitinides – (Prandin and Starlix)
• Medications that decrease the amount of glucose produced by the liver
• Medications that increase the sensitivity of cells to insulin (Actos and Avandia)
• Medications that decrease the absorption of carbohydrates from the intestine (Precose)
• New medications that effect glycemic control (Symlin and Byetta)
• DPP–IV inhibitors
• Combination medications
• Treatment of diabetes with insulin
• Different methods of delivering insulin
• Pre–filled insulin pens
• Insulin pump
• Inhaled Insulin
• Intranasal, Transderm
• The future of pancreas transplantation
• Diabetes main article including causes, symptoms, complications, and diagnosis
How is diabetes treated?
The major goal in treating diabetes is to minimize any elevation of blood sugar (glucose) without causing abnormally low levels of blood sugar. Type 1 diabetes is treated with insulin, exercise, and a diabetic diet. Type 2 diabetes is treated first with weight reduction, a diabetic diet, and exercise. When these measures fail to control the elevated blood sugars, oral medications are used. If oral medications are still insufficient, treatment with insulin is considered.
Adherence to a diabetic diet is an important aspect of controlling elevated blood sugar in patients with diabetes. The American Diabetes Association (ADA) has provided guidelines for a diabetic diet. The ADA diet is a balanced, nutritious diet that is low in fat, cholesterol, and simple sugars. The total daily calories are evenly divided into three meals. In the past two years, the ADA has lifted the absolute ban on simple sugars. Small amounts of simple sugars are allowed when consumed with a complex meal. For more, please read the Diabetic Diet article.
Weight reduction and exercise are important treatments for diabetes. Weight reduction and exercise increase the body's sensitivity to insulin, thus helping to control blood sugar elevations. For more, please read the Weight Loss and Fitness articles.
Medications for type 2 diabetes
WARNING: All the information below applies to patients who are not pregnant or breastfeeding. At present the only recommended way of controlling diabetes in women who are pregnant or breastfeeding is by diet, exercise and insulin therapy. You should speak with your doctor if you are taking these medications and are considering becoming pregnant or if you have become pregnant while taking these medications.
Based on what is known, medications for type 2 diabetes are designed to:
1. Increase the insulin output by the pancreas.
2. Decrease the amount of glucose released from the liver.
3. Increase the sensitivity (response) of cells to insulin.
4. Decrease the absorption of carbohydrates from the intestine.
5. Slow emptying of the stomach to delay the presentation of carbohydrates for digestion and absorption in the small intestine.
When selecting therapy for type 2 diabetes, consideration should be given to:
1. The magnitude of change in blood sugar control that each medication will provide.
2. Other coexisting medical conditions (high blood pressure, high cholesterol, etc.)
3. Adverse effects of the therapy
4. Contraindications to therapy
5. Issues that may affect compliance (timing of medication, frequency of dosing)
6. Cost to the patient and the healthcare system
It's important to remember that if a drug can provide more than one benefit (lower blood sugar and have a beneficial effect on cholesterol, for example), it should be preferred. It's also important to bear in mind that the cost of drug therapy is relatively small compared to the cost of managing the long–term complications associated with poorly controlled diabetes.
Varying combinations of medications also are used to correct abnormally elevated levels of blood glucose in diabetes. As the list of medications continues to expand, treatment options for type 2 diabetes can be better tailored to meet an individuals needs. Not every patient with type 2 diabetes will benefit from every drug, and not every drug is suitable for each patient. Patients with type 2 diabetes should work closely with their physicians to achieve an approach that provides the greatest benefits while minimizing risks.
Patients with diabetes should never forget the importance of diet and exercise. The control of diabetes starts with a healthy lifestyle regardless of what medications are being used.
Medications that increase the insulin output by the pancreas – sulfonylureas and meglitinides
Sulfonylureas
Historically, increasing insulin output by the pancreas has been the major area targeted by medications used to treat type 2 diabetes. Medications that increase the output of insulin belong to a class of drugs called sulfonylureas. Sulfonylureas primarily lower blood glucose levels by increasing the release of insulin from the pancreas. Older generations of these drugs include chlorpropamide and tolbutamide, while newer drugs include glyburide (DiaBeta), glipizide (Glucotrol), and glimepiride (Amaryl). These drugs are effective in rapidly lowering blood sugar but run the risk of causing hypoglycemia (abnormally low and dangerous levels of blood sugar). In addition, they are sulfa–containing drugs and should be avoided by patients who are allergic to sulfa .
Meglitinides – repaglinide (Prandin) and nateglinide (Starlix)
The class of drugs known as meglitinides is relatively new. Meglitinides also work on the pancreas to promote insulin secretion. Unlike sulfonylureas that bind to receptors on the insulin producing cells, meglitinides work through a separate potassium based channel on the cell surface. Unlike the sulfonylureas which last longer in the body, repaglinide (Prandin) and nateglinide (Starlix) are very short acting, with peak effects within one hour. For this reason, they are given up to three times a day just before meals. Since these drugs also increase circulating insulin levels, they may cause hypoglycemia, but the literature suggests this is less frequent than the hypoglycemia seen with sulfonylureas.
Prandin
In a three month study, repaglinide (Prandin) dropped fasting blood glucose values by 61 mg/dL and post meal blood glucose values by 100 mg/dL. Because Prandin is short acting and given before meals, it is particularly beneficial in lowering blood glucose after meals and does not tend to lower fasting glucose levels to the same degree. Prandin has been used in combination with other medications, such as metformin (Glucophage), with impressive results. In 83 patients with type 2 diabetes, blood sugar control improved significantly with the addition of Prandin to Glucophage.
Prandin interacts with other medications. Therefore, the doctor must be aware of all other medications a patient is taking before prescribing Prandin. The usual starting dose is 0.5mg before each meal and can be increased to 4mg. The maximum daily dose is 16mg. Prandin is used with caution in people with kidney or liver abnormalities. Since Prandin increases insulin levels, it has the risk of causing abnormally low blood sugars. Blood sugars that remain severely low can result in sweating, tremors, confusion, and may lead to coma and seizure. In addition, the use of Prandin has been associated with headaches, muscle and joint aches, along with sinus infections in some individuals. This drug should not be used in pregnancy or by nursing mothers. The dose may need to be adjusted in older people, since the elderly may metabolize (eliminate) medications at a slower rate. For more, please read the drug information on repaglinide (Prandin).
Starlix
Nateglinide (Starlix) has essentially the same profile of side effects and interactions as Prandin. The major benefit of Starlix is that the starting dose of 120mg does not need to be adjusted upward, but rather remains constant. These medications are also relatively safe to use in people with impaired kidney function. For more, please read the drug information on nateglinide (Starlix).
Medications that decrease the amount of glucose produced by the liver
A class of drugs called biguanides has been used for many years in Europe and Canada. In 1994, the FDA approved the use of the biguanide metformin (Glucophage) for the treatment of type 2 diabetes in the U.S. Glucophage is unique in its ability to decrease glucose production by the liver. Briefly, because metformin does not increase insulin levels, when used alone, it does not usually cause hypoglycemia. In addition, metformin has an effect whereby it tends to suppress appetite, which may be beneficial in diabetics who tend to be overweight. Metformin may be used by itself or together with other oral drugs or insulin. It should not be used in patients with kidney impairment and should be used with caution in those with liver impairment. The older biguanides that preceded metformin were associated with a serious condition called lactic acidosis, a dangerous acid build up in the blood resulting from accumulation of the drug and its breakdown products. While metformin is safer in this regard, it is recommended that the drug be discontinued for 24 hours before any procedure involving the intravenous injection of dyes (such as for some x–ray studies of the kidney) or surgery is performed. The dyes may impair kidney function and cause a build up of the drug in the blood. Metformin can be restarted after these procedures once the patient is urinating normally.
Medications that increase the sensitivity of cells to insulin
The class of drugs known as thiazolidinediones lowers blood glucose by improving target cell response to insulin (that is, increasing the sensitivity of the cells to insulin). Troglitazone (Rezulin) was the first of this class in the U.S. Because of severe toxic liver effects, troglitazone has been taken off the market. Sister compounds are now available with a better safety profile. These drugs include pioglitazone (Actos) and rosiglitazone (Avandia).
Pioglitazone (Actos) and rosiglitazone (Avandia) are thiazolidinediones approved for use in the U.S. While they are sister compounds to Rezulin, extensive studies have failed to show that they are associated with any liver problems. Both Avandia and Actos act by increasing the sensitivity (responsiveness) of cells to insulin. They improve the sensitivity of muscle and fat cells to insulin. These drugs have been effective in lowering blood sugars in patients with type 2 diabetes, Actos and Avandia act within one hour of administration and are taken once daily. It is important to note that it takes up to six weeks to see a drop in blood glucose levels with these drugs and up to 12 weeks to see a maximum benefit. Actos and Avandia have been approved as first line therapy in diabetes and for use in combination with other drugs. Both drugs may be used in patients taking other oral drugs as well as those using insulin.
While reported liver problems with these agents are mild (and reversible with discontinuation of the drug), most physicians choose to follow an earlier recommendation to do blood tests to detect liver injury every two months or so during the first year of therapy. Recently this recommendation has been removed. If at any point the liver tests increase to three times the normal upper limit, the drug should be stopped.
The most important contraindications to these medications include any type of liver disease, and heart failure. Fluid retention can be of particular concern in patients with signs or symptoms of heart failure and in those with ejection fractions of less than 40% which indicates poor function of the heart. While the reports are three to eight pounds, clinical experience shows up to 12–15 pounds of weight gain can occur. Usually the majority of this is fluid, but an absolute body weight gain can also occur. This is likely to be dose–dependent and, therefore, the increases in weight may be greater with higher doses of drug. Weight gain is more pronounced in patients who are also taking insulin. In general, the ankle swelling and puffiness due to the accumulation of fluid can be controlled with the addition of a diuretic such as spironolactone (Aldactone) — (furosemide (Lasix) does not work as well) — or by reducing the dose. On occasion, patients may be symptomatic enough from fluid retention to warrant withdrawal of the drug. Some recent studies have suggested an association between pioglitazone and rosiglitazone and untoward cardiac events, for example, heart attacks, though this association is controversial. Regardless of the controversy, it is well established that pioglitazone and rosiglitazone should be avoided in patients with symptomatic heart failure or heart failure.
Another newer concern is an association of treatment with a small increase in the frequency of fractures of the distal long bones of the arms and legs. At present, this does not translate into fractures of the hip and spine, which would be clinically more worrisome. More data is needed to make a definitive statement about cause and effect at this time.
As an aside, Actos and Avandia have an added benefit of changing cholesterol patterns in diabetes. HDL (or good cholesterol) increases with these medications, and triglycerides often decrease. While there is some controversy regarding what happens to bad cholesterol (LDL) levels, there is a suggestion that Actos may be superior in changing lipid profiles than Avandia. In this population of diabetics that is already at an increased risk for heart disease, an improvement in cholesterol profile is beneficial. As more and more data becomes available, there is mounting evidence that this class of drugs may provide direct benefits to the heart and large blood vessels and may actually be valuable in preventing the progression of diabetes in high–risk individuals by reducing inflammation and by decreasing clotting factors. As time goes on, I have no doubt that the uses for this class of medications will expand. For more, please read the drug information on pioglitazone (Actos) and rosiglitazone (Avandia).
Medications that decrease the absorption of carbohydrates from the intestine
Before being absorbed into the bloodstream, carbohydrates must be broken down into smaller sugar particles, such as glucose, by enzymes in the small intestine. One of the enzymes involved in breaking down carbohydrates is called alpha glucosidase. By inhibiting this enzyme, carbohydrates are not broken down as efficiently and glucose absorption is delayed.
Precose
The name of the alpha glucosidase inhibitor available in the U.S. is acarbose (Precose). In clinical trials with over 700 patients, the use of Precose was associated with a reduction in hemoglobin A1c values (a well known measurement of average blood sugars over the preceding three months) that was significantly greater than the use of placebo (no treatment). However, as a single agent, Precose is not as effective as the other medications for diabetes. Since Precose works in the intestine, its effects are additive to diabetic medications that work at other sites, such as sulfonylureas. Clinical studies have shown statistically better control of blood glucose in patients treated with Precose and a sulfonylurea compared to the sulfonylurea alone. Precose is currently used alone or in combination with a sulfonylurea.
Precose is taken three times a day at the beginning of meals. The dosage varies from 25 to 100mg with each meal. The maximum recommended dose is 100mg three times a day. At doses greater than this, reversible abnormalities in liver tests may be seen. Because of its mechanism of action, Precose has significant gastrointestinal side effects. Abdominal pain, diarrhea, and gas are common and are seen in up to 75% of patients taking Precose. For this reason, Precose is administered using a low initial dose that is increased over weeks depending on the patient's tolerance. Most of the gastrointestinal symptoms tend to subside over the course of a few weeks although some patients report persistent problems. For more information, please read the drug information on acarbose (Precose).
New medications that effect glycemic control
Symlin (pramlintide)
Symlin is the first in a new class of injectable, anti–hyperglycemic medications for use in patients with type 2 or type 1 diabetes treated with insulin. Pramlintide, the active ingredient in Symlin, is a synthetic analog of human amylin, a naturally occurring neuroendocrine hormone synthesized by pancreatic beta cells that helps control glucose control after meals. Amylin, similar to insulin, is absent or deficient in patients with diabetes. When used with insulin, this compound can improve glycemic control and has additional benefits that cannot be realized with insulin alone.
According to published data, Symlin reduces post meal blood sugar peaks, reduces glucose fluctuations throughout the day, enhances satiety (the sensation of fullness) leading to potential weight loss, and lowers mealtime insulin requirements. Studies have shown it improves A1C beyond the effect of insulin alone.
Symlin is taken just prior to meals, three times a day. It is given in injection form and is used for:
• Type 2 diabetes, as an additional treatment in patients who use mealtime insulin therapy and have failed to achieve desired glucose control despite optimal insulin therapy, with or without a concurrent sulfonylurea agent and/or metformin.
• Type 1 diabetes, as an additional treatment in patients who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy.
Symlin is considered a therapy option in patients with insulin–using type 2 or type 1 diabetes, that are unable to achieve adequate glycemic control despite individualized insulin management. Insulin–using patients with type 2 diabetes may also be taking a concurrent sulfonylurea agent and/or metformin.
The major side effect of Symlin is nausea, and this can be reduced with a slow, steady, increase in dose. The other major side effect is hypoglycemia (dangerously low levels of blood sugar). To avoid this, the dose of mealtime insulin should be cut in half when starting Symlin. Of note is the degree of weight loss seen with Symlin therapy. Studies for up to six months show weight loss of greater than six pounds more than placebo (inactive pills). For more, please read the drug information on pramlintide (Symlin).
Byetta (exenatide)
Byetta (exenatide) is a new medication on the market that has it's origins in an interesting place––the Gila monster's saliva. Scientists studying this small lizard noted it could go a long time without eating. They found a substance in it's saliva that slowed stomach emptying, thus making the lizard feel fuller longer. This substance was similar in nature to a gut hormone found in humans known as GLP–1. GLP–1 is broken down in the body by an enzyme called DPP–IV. So, if you could make a substance like GLP–1 that was not so easy to breakdown, this would have potential benefit; thus, the studies began. Ultimately, after modifying this hormone, exenatide (with the trade name Byetta) was developed. Byetta is the first in a new class of drugs for the treatment of type 2 diabetes called incretin mimetics. Byetta has been shown to have many of the same effects on sugar regulation as GLP–1, so it mimics the body's natural physiology for self–regulating blood sugar. Namely, it slows the release of glucose from the liver, slows stomach emptying thereby regulating delivery of nutrients to the intestine for absorption, and works centrally in the brain to regulate hunger.
Byetta is indicated as additional therapy to improve control of blood sugars in patients with type 2 diabetes who are taking metformin, a sulfonylurea, or a combination of metformin and a sulfonylurea but who have not achieved adequate sugar control. It enhances the way the insulin producing beta cells in the pancreas work. Insulin secretion increases only when blood sugars are high and decreases as blood sugars approach normal. In addition to enhancing the normal physiology of the beta cell, Byetta suppresses glucose release from the liver, slows stomach emptying and the absorption of nutrients including carbohydrate, and reduces intake of food.
Just like Symlin, Byetta is given by injection, but it is given twice a day (usually before breakfast and dinner meals). It comes in a disposable pen form and is available in two doses. The goal is to start with the lower dose for a month or so and then move up to the higher dose if needed and if tolerated. Similar to Symlin, the main side effect is nausea, most likely due to its effects on stomach emptying. This medication is temperature sensitive and it was recommended that the pens be stored at 36–46 degrees F. Recently, this has changed, with a recommendation that unopened pens be refrigerated, and once opened, the pens can be left at room temperature. The risk of hypoglycemia is still a possibility with Byetta, especially when used in combination with sulfonylureas. Your physician may choose to decrease the dose of some of your other medications when initially evaluating how you respond to Byetta.
Similar to Symlin, weight reduction is seen with Byetta in the majority of patients. This makes it particularly suitable for the typical patient with type 2 diabetes who is also overweight. For more, please read the drug information pamphlet on exenatide (Byetta).
A longer acting from of Byetta is currently being considered for approval by the FDA. This would allow for the same benefits (and side effects) without need for such frequent injections.
DPP–IV inhibitors
GLP–1 in the body is broken down by an enzyme called DPP IV. Logically, you can either make a synthetic GLP–1 that is not broken down by this enzyme (for example, Byetta) OR you could try to stop the enzyme that breaks down the GLP–1 your body already makes. Hence, the new class of drugs called DPP IV inhibitors. They do just that, that is, they inhibit this enzyme from breaking down GLP–1. This allows GLP–1 already in the blood to circulate longer. There are a number of companies working on this class of drug and the FDA just approved the first drug in this class made by Merck and called Januvia. Januvia can be used in combination with certain other medications and must be dose adjusted in patients with poor kidney function. For more, please read the Januvia pamplet.
These drugs have essentially the same side effect profile as Byetta; however, they are in pill form. While Byetta has a significant weight loss profile, DPP–IV inhibitors so far have had no effect on weight.
Combination medications
Glyburide/metformin (Glucovance), rosiglitazone/metformin (Avandamet), glipizide/metformin (Metaglip), and pioglitazone/metformin (Actosplusmet) are four relatively new combination pills that are on the market to treat diabetes.
• Glucovance combines glyburide with metformin in varying doses.
• Avandamet is a combination of varying doses of Avandia and metformin.
• Actosplusmet is a combination of varying doses of pioglitazone and metformin.
• Metaglip is a combination pill containing glipizide and metformin in varying strengths.
The benefit to these combination drugs is that there are fewer pills to take, hopefully leading to better compliance. While they work well, I personally like to give patients individual medications until I know what doses are working, and then switch to a combination pill once the patient has been stable on the doses of individual medications for a period of time.
Treatment of diabetes with insulin
Insulin is the mainstay of treatment for patients with type 1 diabetes. Insulin is also important in type 2 diabetes when blood glucose levels cannot be controlled by diet, weight loss, exercise, and oral medications.
Ideally, insulin should be administered in a manner that mimics the natural pattern of insulin secretion by a healthy pancreas; however, the complex pattern of insulin secretion by the pancreas is difficult to duplicate. Still, adequate blood glucose control can be achieved with careful attention to diet, regular exercise, home blood glucose monitoring, and multiple insulin injections throughout the day. For more, please see the Diabetes and Home Care Monitoring article.
In the past, the insulin was being derived from animal sources, particularly cows and pigs. Not only was there a problem with enough supply of insulin to meet the demand, but beef and pork insulin also had specific problems. Originating from animals, these types of insulin caused immune reactions in some people. Patients would become intolerant or resistant to animal insulin. With the acceleration of scientific research in the latter half of the twentieth century, beef and pork insulin were replaced by human insulin. In 1977, the gene for human insulin was cloned, and through modern technology, manufactured human insulin was made available. Human insulin is now widely used.
Insulin now comes in a variety of preparations that differ in the amount of time following injection until they begin to work and the duration of their action. Because of these differences, combinations of insulin are often used to allow for a more tailored regimen of blood sugar control. The table below lists the most common types of insulin currently in use in the U.S. and their specific properties.
Name of Insulin Onset of Action Peak Effect After Injection
Humalog and Novolog//Very Short Acting 5–15 minutes 30–60 minutes
Regular/Short Acting 30 minutes 2–5 hours
NPH/Intermediate Acting 1–2.5 hours 8–14 hours
Lente/Intermediate Acting 1–2.5 hours 8–12 hours
Ultra Lente/Long Acting 4–6 hours 10–18 hours
Lantus 2–3 hours Stable from 2–3 hours to @20 hours
Detemir 3–4 hours Dose dependent (longer acting at higher doses)
Combinations – 75/25, 70/30, 50/50 30 minutes 7–12 hours
For example, a patient may take an injection of Lantus in the morning and evening to provide a baseline of insulin throughout a 24–hour period. In addition, the same patient may take an injection of Humalog just before meals to cover the increase in carbohydrate load after eating.
Different methods of delivering insulin
Not only is the variety of insulin preparations growing, so are the methods for administering insulin.
Pre–filled insulin pens
In the past, insulin was available only in an injectable form that involved carrying syringes (which a few decades ago were made of glass and required sterilization), needles, vials of insulin, and alcohol swabs. Needless to say, patients often found it difficult to take multiple shots each day, and, as a result, good blood sugar control was often compromised. Many pharmaceutical companies are now offering discreet and convenient methods of delivering insulin.
Both Novo Nordisk and Lily have an insulin pen delivery system. This system is similar to an ink cartridge in a fountain pen. A small pen–sized device holds an insulin cartridge (usually containing 300 units). Cartridges are available in the most widely used insulin formulations, such as those listed in the table above. The amount of insulin to be injected is dialed in by turning the bottom of the pen until the required number of units is seen in the dose–viewing window. The tip of the pen consists of a needle that is replaced with each injection. A release mechanism allows the needle to penetrate just under the skin and deliver the required amount of insulin. The cartridges and needles are disposed of when finished and new ones simply are inserted. In many cases, the entire pen is disposed of. These insulin delivery devices are less cumbersome than traditional methods.
Insulin pump
The most recently available advance in insulin delivery is the insulin pump. In the U. S., MiniMed, Deltec and Disetronic market the insulin pump. An insulin pump is composed of a pump reservoir similar to that of an insulin cartridge, a battery–operated pump, and a computer chip that allows the user to control the exact amount of insulin being delivered. Currently, pumps on the market are about the size of a pager or beeper. The pump is attached to a thin plastic tube (an infusion set) that has a cannula (like a needle but soft) at the end through which insulin passes. This cannula is inserted under the skin, usually on the abdomen. The cannula is changed every two days. The tubing can be disconnected from the pump while showering or swimming. The pump is used for continuous insulin delivery, 24 hours a day. The amount of insulin is programmed and is administered at a constant rate (basal rate). Often, the amount of insulin needed over the course of 24 hours varies depending on factors like exercise, activity level, and sleep. The insulin pump allows for the user to program many different basal rates to allow for this variation in lifestyle. In addition, the user can program the pump to deliver additional insulin during meals to cover the excess demands for insulin caused by the ingestion of carbohydrates with the meal.
Over 50,000 people worldwide are using an insulin pump. This number is growing dramatically as these devices become smaller and more user–friendly. Insulin pumps allow for tight blood sugar control and lifestyle flexibility while minimizing the effects of low blood sugar (hypoglycemia). At present, the pump is the closest device on the market to an artificial pancreas. More recently, newer models of the pump have been developed that do not require a tubing, in fact - the insulin delivery device is placed directly on the skin and any adjustments needed for insulin delivery are made through a PDA like device that must be kept within a 6 foot range of the insulin delivery device, and can be worn in a pocket, kept in a purse, or on a tabletop when working.
Probably the most exciting innovation in pump technology is the ability to use the pump in tandem with newer glucose sensing technology. Glucose sensors have improved dramatically in the last few years, and are an option for patients to gain further insight into their patterns of glucose response to tailor a more individual treatment regimen. The newest generation of sensors allows for a real time glucose value to be given to the patient. The implantable sensor communicates wirelessly with a pager-sized device that has a screen. The device is kept in proximity to the sensor to allow for transfer of data, however, it can be a few feet away and still receive transmitted information. Depending on the model, the screen displays the blood glucose reading, a thread of readings over time, and a potential rate of change in the glucose values. The sensors can be programmed to produce a "beep" if blood sugars are in a range that is selected as too high or too low. Some can provide a warning beep if the drop in blood sugar is occurring too quickly.
To take things one step further, there is one particular sensor that is new to the market that is designed to communicate directly with the insulin pump. While the pump does not yet respond directly to information from the sensor, it does "request" a response from the patient if there is a need for adjustments according to the patterns it is programmed to detect. The ultimate goal of this technology is to "close the loop" by continuously sensing what the body needs, and then responding by providing the appropriate dose of insulin. While this technology is a few more years in the making, the strides in this direction continue to grow.
Inhaled Insulin
Inhaled insulin, marketed by Pfizer in 2006, was approved by the FDA. This inhaled form of insulin is called Exubera. The insulin is packaged in dry blister packs that are inserted into an inhalation device. This device lances the powder packs allowing the insulin to enter a chamber that has a mouth piece through which the user can inhale the insulin. Exubera has a peak of action similar to Humalog (rapid acting), and a duration of action similar to regular insulin (short acting). It can be combined with oral medication in patients with type 2 diabetes or used alone. In patients with type 1 diabetes the insulin should be combined with a longer acting basal insulin such as glargine.
The side effect profile of inhaled insulin is similar to other insulins, and the user must be aware of hypoglycemia. In addition, since the insulin is absorbed through the lungs, there was initial concern regarding lung function. While there is a slight decrease in lung function with the initial use of Exubera, this stabilizes quickly and returns to baseline of aged matched controls when the Exubera is discontinued. Since this is still a new product, it is recommended that any patient starting on inhaled insulin have lung function tests done prior to starting treatment. If baseline values of FEV1 (a measure of lung function) are < 70%, Exubera is not given. After six months of use lung function tests are performed again; if deterioration is noted, Exubera is discontinued.
Exubera is not to be used in regular or intermittent smokers and patients requiring very small doses of insulin. Nevertheless, in the right population, this is a great option.
Note: Unfortunately, acceptance of Exubera was poor over the year or so it was available since it's launch in 2006. Recently in October 2007, the company Pfizer decided not to sell the product anymore. Part of this issue was the time required to teach the device and the uniqueness of the format of delivery. While no major medical concerns were noted with it's use, it simply has not been accepted by patients and doctors. Perhaps we will see this modality come back in a new easier to use incarnation.
Intranasal, Transdermal
Other routes for the delivery of insulin have also been tried. Intranasal insulin delivery was thought to be promising. However, this method was associated with poor absorption and nasal irritation. Transdermal insulin (skin patch delivery) has also yielded disappointing results to date. Insulin in pill form is also not yet effective since the digestive enzymes in the gut break it down.
The future of pancreas transplantation
Ultimately, the goal in the management of type 1 diabetes is to provide insulin therapy in a manner that mimics the natural pancreas. Perhaps the closest therapy available at this time is a transplant of the pancreas. Several approaches to pancreatic transplantation are currently being studied, including the whole pancreas and isolated islet cells (these groups of cells contain beta cells that are responsible for insulin production). Data available from 1995 indicates that almost 8,000 patients underwent pancreatic transplantation. Most patients undergo pancreatic transplantation at the time of kidney transplantation for diabetic kidney disease.
Transplantation is not without risk. Both the surgery itself and the immunosuppression that must occur afterward pose significant risks to the patient. For these reasons, the kidney and pancreas are usually transplanted at the same time. At present, there is disagreement about whole pancreas transplantation in patients not currently requiring kidney transplantation. The issue of whether the benefits outweigh the risks in these patients is under debate. There is also a chance that diabetes will occur in the transplanted pancreas. Selectively transplanting islet cells is an interesting alternative to whole pancreas transplantation. However, the concern over rejection remains. Attempts to disguise the islet cells in tissues that the body won't reject (for example, by surrounding the islet cells by the patient's own cells and then implanting them) are underway. In addition, researchers are exploring artificial barriers that can surround the islet cells, provide protection against rejection, and still allow insulin to enter the bloodstream.
A Final Word
These last few years have been an exciting time in diabetes care. Many agents for the treatment of type 2 diabetes are under development and the options for insulin therapy continue to grow and methods for insulin delivery continue to become more refined. While research continues to expand in these areas, one thing remains constant. Achieving the best blood sugar control possible remains the ultimate goal in both type 1 and type 2 diabetes. We now know, beyond a doubt, that good blood sugar control minimizes the long–term complications of diabetes, including blindness, nerve damage, and kidney damage. Finally, a healthy lifestyle can do nothing bad...it should remain the cornerstone of management for diabetes.