At the European Association for the
Study of Diabetes Annual Meeting, a great amount of discussion is
going on about the role of the beta cell in the pathogenesis of type
2 diabetes and how we are going to work to prevent the progressive
loss of beta-cell function and mass that characterizes the disease.
Everybody recognizes that the beta cell
is the key feature of why we get hyperglycemia as well as why we see
a progression of the disease. With the approaches we are currently
using, this disease results in a progressive loss of the ability of
the beta cell to secrete insulin, along with loss of the beta cells
that are responsible for making this critical hormone.
Many different approaches have been
used until now to try to prevent this loss of beta-cell function. We
have a variety of classes of agents that have addressed the beta cell
directly as well as indirectly, perhaps by reducing the load of the
beta cell so that the demand for it to produce and secrete insulin is
decreased.
What has been learned through many of
these interventions is that although we can maintain glycemic control
for a period of time, inevitably there will be progression and we
will need to add agents. Every patient with type 2 diabetes has
beta-cell dysfunction, and every patient with type 2 diabetes needs
to be aggressively treated to slow progression.
The different agents that have been
used seem to have variable degrees of ability to slow progression.
For example, the sulfonylureas, while being capable of stimulating
insulin secretion, seem to drive the beta cell towards that
inevitable loss of function far more rapidly than other approaches
such as metformin or the thiazolidinediones.
In fact, if an individual were to live
long enough, every patient with type 2 diabetes will have ultimate
beta-cell failure that requires insulin-replacement therapy. We are
losing patients to cardiovascular disease even with the more
aggressive control of blood pressure and lipids, many of them before
they have progressed to beta-cell failure.
The challenge is to come up with new
approaches that would allow us to slow this progression. The
traditional thinking, where one provides agents that stimulate the
cell to secrete insulin, may not be optimal. We may need to start
thinking of new approaches that would allow the beta cell to rest
some and, therefore, be able to live longer.
Studies looking at individuals with
prediabetes have identified that the beta cell is already defective.
With interventions that improve insulin sensitivity, we can typically
slow the progression of diabetes. Similarly, if we intervene in
individuals with diabetes to reduce the demand on the beta cells with
approaches as simple as aggressive lifestyle changes, we can slow
progression.
We need to clearly focus on these areas
to try to prevent our patients from getting progressive hyperglycemia
due to progressive beta-cell loss and, ultimately, the diabetic
complications that we traditionally see with the disease.
We've been seeing recently that a
number of the agents that are used to treat type 2 diabetes,
including GLP-1 receptor agonists and SGLT2 inhibitors, may offer
hope in reducing diabetic complications in individuals with very
advanced disease. Although this is very useful information, we have
yet to fully understand how this is happening. The challenge for all
of us is to find approaches that can be used earlier in the disease,
perhaps with these classes of agents or others that would not allow
us to worry about late-stage disease.
In my mind, the beta cell is the
key. We are going to have to aggressively target it. We don't
necessarily have to target it by stimulating it as much as resting
it.
Every patient with type 2 diabetes has
beta-cell dysfunction, and every patient with type 2 diabetes needs
to be aggressively treated to slow progression. Failure to treat our
patients aggressively is going to allow accelerated progression and
ultimately result in failure and insulin therapy.
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