Clamping
down: How tight should glycemic control be?
By Anne Paxton, March 2002,
Feature Story
Like the Red
Queen in Lewis Carroll's
Through the Looking Glass, clinicians are running as hard
as they can just to stay in place when diagnosing diabetes
mellitus. Of the 16 million Americans with diabetes, more than
five million are unaware they have it. Clinicians now diagnose
some 800,000 new cases of Type 2 diabetes annually, but with the
incidence of diabetes having tripled in the last 30 years, they
still may be falling behind.
The surge in
diabetes prevalence has sharpened concern that guidelines for
screening and managing this deadly and costly disease are not
stringent enough. "We need more aggressive, complete, and
cohesive standards," contends Rhoda Cobin, MD, president of the
American Association of Clinical Endocrinologists.
The causes
of the escalation in diabetes cases are fairly well known. "The
frequency and severity of obesity are rising, and at the same
time, the population is becoming more and more sedentary," says
William E. Winter, MD, professor of pathology and pediatrics at
the University of Florida. "This is causing a high frequency of
the population to be affected with insulin resistance, a
precursor of Type 2 diabetes."
The numbers
show a dangerous lag time between when the disease is contracted
and when it is diagnosed. Many newly diagnosed patients have had
the disease, undetected, for 10 years, and half of them are
experiencing complications by the time they are diagnosed.
Can these
patients be detected earlier? And should there be changes in how
they are monitored? Those were pivotal questions behind a
consensus conference of world experts in diabetes convened by
the American College of Endocrinology. Agreeing that more
aggressive screening and monitoring are needed, the conference,
held last August, set forth three recommendations to change
guidelines for glycemic control in people with diabetes and put
them in line with guidelines already in force in Europe:
-
Start
screening people at high risk for the disease at age 30, which
is 15 years earlier than is currently recommended by the
American Diabetes Association.
-
Lower HbA1c
(termed A1c in the recommendations) target levels
for diabetes control from seven percent to 6.5 percent.
-
Lower
target levels of preprandial blood glucose to 110 (ADA's
range, 90-130) and establish a target level of 140 for
postprandial blood glucose.
The
Association of Diabetes Educators has already endorsed the new
guidelines. The cornerstone group, the ADA, says it is
considering them, as is the National Institute of Diabetes and
Digestive and Kidney Diseases, a key federal agency involved in
diabetes.
In a
presentation at the 2001 ASCP/CAP meeting, Dr. Winter confirmed
that the latest refinement of diabetes testing guidelines is
part of a continuing debate about the value and complexities of
glycemic control. For example, there has not been unanimous
support for the most recent lowering of the fasting plasma
glucose cutoff, from 140 mg/dL to 126 mg/dL, a change the ADA
endorsed in 1997.
"There's
been controversy since that time as to whether the cut point was
actually too low," Dr. Winter says. "Some people believe that it
should still be 140 mg/dL because many people who don't yet have
complications would still be defined as diabetic."
At the time,
the ADA offered several arguments in favor of a lower cut point.
"First," says Dr. Winter, "a sizable portion of Type 2 patients
already had microvascular complications at the time of
diagnosis. So if one waited to 140 mg/dL or above—the pre-1997
cutoff—one could actually delay or miss the diagnosis. Second,
there's no cut point below which there's a 100 percent chance of
not having complications. It's possible to have complications
even with an average blood glucose of less than 140 mg/dL."
Third, when
researchers looked at the numbers of people being diagnosed with
Type 2 diabetes and compared them with the population frequency
of diabetes, they found the 140 mg/dL cut point was not as
sensitive as the two-hour oral glucose tolerance test cutoff of
200 mg/dL. By lowering the cut point to 126 mg/dL, they would
increase the sensitivity of the test and pick up a group that
would otherwise have been missed.
The hard
reality of diabetes diagnosis is that even these cutoffs may be
too high, says Dr. Winter. Microvascular complications like
retinopathy and nephropathy, which can cause blindness or kidney
failure, are one thing. But serious macrovascular complications,
including coronary artery disease, cerebrovascular disease, and
peripheral vascular disease, may develop prior to microvascular.
Fifty percent of Type 1 diabetes patients eventually die of
macrovascular disease, as do 80 percent of Type 2 patients.
This, in
part, explains the greater concern over false negatives than
false positives in diagnosing diabetes. "The minimal requirement
to document hyperglycemia on at least two occasions should
protect patients from being misdiagnosed as diabetic," Dr.
Winter says.
To test for
diabetes, excluding situations where ketoacidosis or nonketotic
hyperglycemic coma are present, outpatients should be in their
general state of health without recent hospitalizations or
changes in diet or exercise. That's because diabetes, a state of
chronic hyperglycemia, must be distinguished from transient
hyperglycemia. Reversible pancreatic islet ß-cell dysfunction or
dysfunctional autonomic control of pancreatic islets, for
example, may cause transient hyperglycemia. "Chronic
pancreatitis can clearly lead to diabetes, but with acute
pancreatitis, you can have a transient dysfunction. So
clinicians just need to be careful," Dr. Winter says.
Other
potential causes of transient hyperglycemia are severe head
trauma, increases in anti-insulin "stress" hormones—which could
go along with recent hospitalization for acute myocardial
infarction, burns, or severe stress—or iatrogenic etiologies
such as use of diabetogenic medications, or excessive rates of
parenteral glucose infusion from intravenous glucose infusions
or hyperalimentation, he says.
"This is not
to say that physicians should ignore hyperglycemia in
hospitalized patients," notes Dr. Winter. "And they may very
well need to treat a non-diabetic individual with insulin if
they are sufficiently hyperglycemic. But if a physician is
worried about a patient who may be diabetic, it would be prudent
to follow up in a number of weeks. The take-home message is, if
the patient recovers from the illness, the physician may need to
retest for hyperglycemia."
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