Type 1 Diabetes Mellitus

You sit in your new diabetes doctor’s waiting room. Your name is called and you are ushered into the examination room. The doctor walks in and before he sits down he asks you: “What type of diabetes do you have?” Panic sweeps you; first question and I flunked already! You manage a meek: “How many types are there? I didn’t realize there is more than one.” No one has asked you that question before.

The doctor tries to reassure you that this is not the first time he sees a patient who didn’t know. So, you try to relax and listen to his explanation.

There are actually several types of diabetes mellitus. The three most common ones in the U.S. are so-called type 1, type 2 and gestational diabetes. The last one is easy, that is diabetes diagnosed during pregnancy. All types of diabetes are diagnosed the same way: glucose (“sugar”) levels in the blood are high (over 126 mg/dl in the fasting state and/or over 200 mg/dl two hours after you eat or drink the “Glucola” in the lab; it is recommended these numbers are obtained on two separate days before the diagnosis is made).

So, what is the difference between types 1 and 2? Type 1 diabetes is a so-called autoimmune condition. That means your own body produces antibodies against parts of the only cells which can make insulin in humans (that is beta cells of the pancreatic islets of Langerhans), eventually destroying them. As a consequence, patients with type 1 diabetes need to administer insulin for the rest of their lives (people cannot live without insulin, so important is the hormone for many functions of your cells and tissues).

Type 2 diabetes, by the way, is that condition in which persons cannot make sufficient amounts of insulin and on top of it the insulin they do manage to make does not do a very good job taking care of things, resulting in high blood glucose levels. There are perhaps twenty times as many people with type 2 than with type 1 diabetes in our country.

Back to type 1 diabetes. A long time ago, it used to be called “juvenile-onset” diabetes because it was thought that it affected only children and adolescents. We know better now. Type 1 diabetes can occur at any age; it’s just that it tends to be more aggressive (there are more antibodies destroying those beta cells quicker) in young people. Also, since it might take five to eight years before the job of destroying those insulin-producing cells is done, it is quite unusual to see type 1 diabetes in infants or very young kids. The other confusing thing is that, thanks to our current lifestyle, people with type 1 diabetes tend not to be skinny any longer. Add to it that because of childhood obesity and physical inactivity we now see many kids being diagnosed with type 2 diabetes, thus blurring the distinction between the diabetes types even more. Type 1 diabetes does not tend to “run in the families” as much as type 2 does even though there are specific genes identified with giving you the increased chance of coming down with type 1 diabetes. However, it is clear your genes alone don’t result in the disease. The unanswered question is what else happens that triggers the onslaught which kills off those insulin-making cells? It has been noticed that the frequency of type 1 diabetes has increased everywhere in the world over the past 100 years. What is it in the environment which might trigger that autoimmune attack in those genetically predisposed individuals? There have been many speculations (you have probably heard of different viruses, cow’s milk, possibly some pollutants or toxic substances in the air) but no definite answers are in. The problem is that even though we could predict type 1 diabetes years before it happens (just by drawing blood for those darn antibodies and measuring how much insulin people make after being given sugar) we can’t screen the entire population every year (imagine how much that would cost!). And since you need to destroy probably as many as 90 percent of those pancreatic cells to see blood sugar go up into the diabetic range, by the time the diagnosis is made it is too late to prevent it.

So, we are stuck (literally) treating type 1 diabetes after it wipes out most of the beta cells; and, the patients then need to take insulin for the rest of their lives. So, the management of type 1 diabetes typically revolves about figuring out the best way to deliver insulin so that glucose (and A1c) levels are as close to normal as possible while minimizing the number of hypoglycemic (low sugar) reactions. Anyone who has tried it will testify how difficult that tightrope walk is. Clearly, educating the patient about the importance of the right diet, physical activity, stress management, proper techniques for checking the blood glucose levels and insulin injection technique, etc. has to be placed on top of the agenda since the tasks can get overwhelming and no one can expect the newly diagnosed patient to know those things right off the bat. The family and community support is essential for successful overall management of this lifelong condition.

Even though every type of insulin will lower blood glucose levels (that is its job after all) in the 21st Century, there are essentially two ways offered to patients with type 1 diabetes: multiple daily insulin injections or continuous insulin infusion by an insulin pump. In both cases, the idea is to copy Mother Nature as closely as possible. In a healthy individual, those beta cells in the pancreas make about half of the insulin continuously— 24 hours a day, 7 days a week, and the other 50 percent come in short bursts to appropriately cover your meals so blood glucose levels always stay normal.

For the multiple insulin shot routine, the “base” is covered by one of two insulin “analogs” (made by changing the structure of human insulin to behave differently), insulin glargine or detemir. Their job is to make sure blood glucose is OK overnight and before each meal. The remaining insulin is provided by mealtime injections of “rapid-acting” analogs (there are three on the U.S. market, insulin LisPro, aspart, and glulisine). Patients usually take as much as needed to “cover” their meals. Most are taught to count carbohydrate content of the meal and match that with the quick-acting insulin (for example, take one unit for every starch exchange or 15 grams of carbohydrate). Insulin pumps provide insulin only in the rapid acting variety. They are worn externally (much as your favorite PDA or cell phone) and push insulin under your skin through a skinny plastic tube all the time. The user programs the pump so it delivers about half as a “basal” rate (that rate varies according to the need), and the remainder gets activated by a push of a button to give bursts (“bolus”) of insulin again to cover the meal. Patients usually change the infusion site every three days. Much progress has been made into making insulin delivery as painless and convenient as possible but it still takes an injection through the skin. Other ways to deliver insulin (into the lungs, through the nose, inhaling into the mouth, skin patches, etc.) have been tried but to date none of them has been judged to be as reliable.

The recent advance has come from using continuous glucose sensors, which give the user real-time information not only about glucose levels but also directions of changes in glucose numbers, history, and can sound alarms for very high or very low readings. Those sensors are placed on the skin and again plastic tubing is inserted under the skin to provide the information.

What about the cure for type 1 diabetes? While many scientists have been working on it for decades, currently, there is none available. The closest we have come is to use pancreas transplant (either whole from a cadaver or a part from a living relative donor) or pancreatic islet cell transplant (in which only the insulin producing cells are injected and they settle around the liver where they start producing insulin normally). Both types of transplants require use of anti-rejection medications by the recipients to avoid rejection of those foreign cells.

As you can see tremendous progress has been made in dealing with type 1 diabetes, but we still have a ways to go…

George Grunberger, MD, FACP, FACE, is chairman of the Grunberger Diabetes Institute in Bloomfield Hills, Michigan, and a Clinical Professor of Internal Medicine and Molecular Medicine & Genetics, Wayne State University School of Medicine in Detroit, Michigan. Dr. Grunberger has published over a hundred original peer-reviewed manuscripts, in addition to review articles, abstracts, book chapters, and letters to journals. His research interests have spanned the spectrum of subjects related to diabetes and its complications, from very basic studies on molecular underpinning of insulin action and insulin resistance to clinical research studies on many aspects of diabetes and its management.