DOCTOR'S VIEW ARCHIVEMedical Author: Ruchi Mathur, MD, FRCP(C)
Medical Editor: Jay W. Marks, MD
The American Diabetes Association's (ADA) annual 66th Scientific Sessions were recently held in Washington DC. The meeting brought close to 18,000 health professionals together to discuss issues related to diabetes (type 1, type 2 and gestational diabetes), prediabetes , metabolic syndrome, and other related disease processes. Topics of interest ranged from trying to understand the pathophysiology of disease (what happens in the body that causes diabetes to develop) to new ways to prevent and treat diabetes including both pharmacotherapy with drugs, and with lifestyle intervention.
The interesting thing about the ADA annual meeting is that many different types of health care providers attend the meetings -- MDs, PhDs, researchers, nutritionists, educators, nurses, and community health workers. Each of these professional groups make a commitment to work together to help treat and prevent diabetes. A team approach is really the only way to attempt to conquer diabetes, which at present affects about 20 million of us in the U. S. alone.
While some of the science presented at symposia was novel and very exciting, particularly advances in beta cell preservation and transplantation (beta cells are the cells that produce insulin) ,I would like to focus on some of the newer therapies that were discussed at the ADA meeting, and tell you about what's up-and-coming in the realm of treatment for diabetes. For the sake of length, I've chosen 3 topics I think will be interesting for the majority of readers: glucose sensors, a new class of drugs called DPP-IV inhibitors and inhaled insulin.
Continuous Glucose Sensors
One of the major advances this year was in the development of technology for continuous glucose sensors. A sensor is a device that is inserted into the subcutaneous fat (just beneath the skin) in the abdomen or upper arm. After calibration with glucose measurements obtained from blood, the sensor then provides real-time glucose readings at five minute intervals. Some of the sensors display a graph for watching trends in blood sugar levels. Other sensors allow for warning beeps to be programmed before blood sugars get too high or to low. Some sensors even calculate the rate of change of blood sugar, allowing a patient to anticipate upcoming hypoglycemic events. Other sensors, such as the model by Medtronic, work especially well with the insulin pump. In this case, the sensor sends a signal directly to the pump which then performs calculations to determine a suggested course of action--which the patient must then approve. A sensor is ideal for patients using insulin pumps, patients prone to large fluctuations in blood glucose, athletes, those with hypoglycemia (particularly at night), or anyone wanting to better understand the relationship between daily activity and food intake with blood glucose levels.
As diabetologists, our goal is to provide our patients with therapies that mimic natural physiology as closely as possible. Aside from successful transplantation or regeneration of the body's insulin producing cells, the ultimate goal is an artificial pancreas that senses the body's sugar level and responds immediately with the appropriate amount of insulin needed to keep blood sugar in the normal range. We are not there yet but are getting closer.
Another area of interest this year stems from the success of a drug released last year know as exenatide (Byetta). Details regarding exenatide can be found by reading the exenatide (Byetta) drug monograph. Basically, it is an injectable, synthetic, incretin-like hormone (similar to an incretin that we humans make ourselves called GLP-1) that works to slow the stomach's emptying, creating a sensation of fullness. It also acts centrally on the brain to promote fullness, on the liver to decrease production of sugar, and on the pancreas to perhaps increase the mass of insulin producing beta cells. Exenatide has the benefit of promoting weight loss in patients (which is a big problem in type 2 diabetes) but has the disadvantage of being in injectable drug requiring injections twice daily.
As mentioned previously, we humans make a similar compound called GLP-1. In diabetes, GLP-1 may not be produced, released or sensed appropriately. In our bodies, there is an enzyme called DPP-IV that breaks down GLP-1 very quickly after it is released. So, the next logical question is; What if we block that enzyme and allow our own GLP-1 levels to increase? Would that work just as well?
Many pharmaceutical companies such as Merck and Novartis are developing such drugs. This class of drugs is known as DPP-IV inhibitors. The real benefit is that the medication is an oral medication that avoids the need for two shots a day. These medications appear to do a good job at controlling blood sugar levels. Alas, as with everything, there is a down side. Unlike exenatide which causes a significant number of patients to loose significant weight, the DPP-IV inhibitors do not appear to have this benefit. They are weight neutral. Another issue this that the enzyme DPP-IV and it's receptor are found in a lot of different tissues throughout the body, and therefore potentially could have effects aside from those that are simply blood sugar related. Basically, we don't know the long-term effects of these compounds since they are so new. DPP-IV inhibitors appear to be promising in helping to control blood sugars in diabetes, but I think that's all we can say for now. They should be on the market within the next year.
All patients with type 1 diabetes require injections of insulin to sustain life. Many patients with type 2 diabetes also need insulin, and of those who don't, about 10% per year ultimately will progress and require insulin. Studies have shown that both physicians as well as patients with type 2 diabetes have a reluctance to start insulin even when it is needed. This delay can result in worsening diabetes complications. Reluctance is often the result of fear of injections and a folklore concern that insulin may cause complications. From the providers perspective, insulin use requires a lot of patient instruction and follow-up, which means spending extra time with a patient.
This year, the FDA approved the release of the first inhaled insulin called Exubera. Exubera is a powdered form of insulin that is delivered to the lungs by way of a special delivery system, somewhat similar to an aerochamber used for asthma medications. The insulin is supplied in blister packs, which are then inserted into the inhaler device. With a trigger squeeze, the blister ruptures, sending the powder insulin into the inhalation chamber for the patient to inhale.
Inhaled insulin is a short acting insulin. If you compare it to injectable insulin, it starts working around the same time as Humalog/Novolog and has a length of action similar to regular insulin. Thus, it is a "prandial" insulin - to be used mostly for meal coverage, and perhaps along with a long acting insulin such as glargine, or with other oral agents in patients with type 2 diabetes. An interesting observation with inhaled insulin is that even though it is short acting, morning fasting blood sugars (after not using the insulin all night) also decreased compared to short acting injectable insulin. The reason for this is not clear.
Studies have shown that the absorption of inhaled insulin is really quite stable within the same subject over time. The exception is with smoking. Smoking actually can increase the amount of insulin absorbed, resulting in the potential for hypoglycemia. Smokers, therefore, are not candidates for inhaled insulin. Other groups such as those with asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis and other chronic lung problems should not use inhaled insulin. Most likely, it will be recommended that patients who are considering the use of inhaled insulin undergo assessment of lung function with pulmonary function tests before starting therapy.
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In the healthy population, there is a slight (not clinically significant) decrease in lung function noted within the first few months of using inhaled insulin. This loss of function does not worsen and, in fact, stabilizes. In studies where inhaled insulin was discontinued, lung function returned to the levels seen in age -matched healthy individuals. The other major side effects of inhaled insulin include cough, however, usually only at the time of inhalation and not persistent.
One of the other concerns with inhaled insulin is dosing. The blister packs are 1 mg and 3 mg which equals about 3 units and 8 units of insulin respectively. Because of the limited dosages, small changes in insulin are not possible. If a patient requires very small doses of insulin, inhaled insulin may not be a good choice for them.
Inhaled insulin is approved for use in the U. S. and will likely come to market by the 4th quarter of 2006.
Over the last few years there has been a fundamental shift in our thinking, and in our goals as providers who treat diabetes. Our primary goal is to prevent disease (complications). Our tools are education, lifestyle interventions, and certain medications targeted at patients with diabetes who are at high-risk for complications. This is a totally separate (and fascinating) discussion.
Our approach to treatment has expanded over the last number of years. We live in an age that provides us with a great and growing number of options for tailoring medication regimens to suit individual patients, and we have tools that allow us to have feedback on our medical choices. Hopefully, the growth in our understanding and treatment of diabetes will translate into improved outcomes for our patients-which is the biggest goal of all!