Gettysburg Medical News
 The Clinical View
 by P.E. Hoffsten, MD
 26 April 2006

DIABETES MELLITUS – I:  WHAT’S WRONG?

            A conservative estimate at this time is that one in ten United States citizens are or will become diabetic in their lifetime.  The expense of this condition in both dollars and in the toll on human comfort is staggering. Diabetes is already the leading cause of kidney failure in our society.  It is the leading cause of blindness in our society and the leading cause of foot amputations.  It is a major contributor to heart attack.  It is a silent condition that leads to significant degenerative changes before the person ever knows that they have the problem.  The next three columns will be devoted to diabetes mellitus.  First, consideration will be given to what is the basic problem with diabetes.  Second column will be devoted to how it can be treated and lastly, I will discuss a new drug called Exanatide which has promise as an additional and new treatment for diabetes.

            First point to realize is that diabetes is a name given to a disease with high blood sugars.  Currently, we believe that blood sugars in the fasting state should be less than 100 mg%.  If a person has a blood sugar from a 100 mg% to 125 mg% in the fasting state, we describe the person as being glucose intolerant.  If the blood sugar is above 126 mg% in the fasting state, they are said to be diabetic.  As anyone could know, these are very arbitrary figures but do provide guidelines so that individuals can be grouped for the purpose of appropriate treatments.

            The individuals with the blood sugar greater than 126 mg% in a fasting state fall into two broad groups.  We first describe the Type I diabetic which used to be called the juvenile onset diabetic. These are individuals that seem to develop a degenerative condition of their insulin secreting cells and lose the ability to make insulin.  We do not know for sure what the cause of this condition is but it seems to represent a viral condition in which susceptible individuals lose their ability to make insulin and become diabetic for that reason.  These individuals require insulin supplementation for the rest of their lives unless they can obtain a successful pancreatic transplant.  These are a very few lucky individuals and the vast majority of type I diabetics require insulin treatment for the rest of their lives.

            The second group of diabetics make up over 90% of all of the diabetics in the United States.  These are the so-called type II diabetics. They used to be called maturity onset diabetics because the disease always seems to occur in adults.

            Where as type I diabetes is basically an insulin deficient state, type II diabetes is an entirely different problem.  The type I diabetic doesn’t have any insulin but the type II diabetic has 2 or 3 or 4 times as much insulin as a normal.  But for reasons that we don’t understand, the insulin in a type II diabetic doesn’t seem to function to lower blood sugars as it normally would.  Thus, the basic problem in a type II diabetic is what is called “insulin resistance”.  The insulin resistance generally begins between age 20 and 50 and is silent for 10 to 20 years.  It is during this time, that degeneration of blood vessels throughout the body occurs.  Finally, when the type II diabetes is diagnosed, the condition often has already resulted in significant changes of the eyes, the kidneys or the nerves of the feet in over half the people when they are diagnosed.  This is the reason that it is so important to catch the diabetic condition early before degenerative changes occur.  Once degenerative changes occur in the eyes or the kidneys or the feet, recovery of the lost function does not occur.  What is gone is gone and you don’t get it back.  It doesn’t work to wait five or six or eight or ten years and say now I am going to control my blood sugars.  Once the eye disease has called blindness, controlling the blood sugar doesn’t give you back your vision or your feet or your kidneys.

            What causes the insulin resistance to occur is still the subject of intensive research but we have learned that there is strong genetic component by which the condition is permitted.  Not every overweight sedentary individual develops diabetes but in those who have the genetic permission, we have learned that overweight and inactivity unmask the genetic predisposition and lead to the disease.

            Once insulin resistance begins to occur, the person’s insulin secreting cells are asked to make more insulin to keep the blood sugar under control.  Initially, this is achieved without difficulty.  But as time passes and the pancreatic insulin secreting cells are asked continuously day in and day out to make two and three and four times the normal amount of insulin, fatigue of the insulin secreting cells occurs.  Then, the insulin secretory rate drops and that is usually when the person becomes diagnosed with being diabetic.  By this time, they have already had the insulin resistance an average of ten years or more and by this time, at least half of the individuals who are then diagnosed already have abnormalities of their eyes, their kidneys or their feet.

            As a group, only one in three diabetics in this country have their blood sugars controlled at a level where degenerative changes are stopped.  Two-thirds of the diabetics in this country do not have control of their blood sugars to a level where their eyes, their feet and their kidneys are protected.

            As if all of this weren’t problem enough, there is one more aspect of the disease that is very discouraging.   Specifically, it appears that as time passes, the insulin secretory capacity of the individual deteriorates further and they make less and less insulin.  Obviously, this leads to higher blood sugars and worsening degenerative changes which produce a snowball like effect.

            When I first diagnose a new diabetic, they almost always say that they will watch their diet and exercise more and correct the problem.  I tell them that diet and exercise will indeed lower blood sugars and decrease the insulin resistance that they have.  But it will not take away the genetic predisposition that they have to become diabetic and it is very unusual that diet and exercise alone are enough to control blood sugars in the normal range.  Thus the critical step to control blood sugars almost always means medications directed to one or another aspect of the disease.    Next week’s column will be devoted to the various medications that are available and the week after to a medication called Exenatide which is new in the past year and presents a number of special therapeutic advantages.