NIH: When most people think about risk factors for cardiovascular disease, they likely think of blood pressure readings or cholesterol levels. But here’s something else that should be high on that list: diabetes. That’s because people with diabetes are roughly twice as likely to die of heart disease than other folks . Yet the issue of how best to help such people lower their cardiovascular risks remains a matter of intense debate. Some studies have suggested that part of the answer may lie in tightly controlling blood sugar (glucose) levels with a strict regimen of medications and monitoring . Other research has shown that the intense effort needed to keep blood glucose levels under tight control might not be worth it and may even make things worse for certain individuals .
Now, a follow up of a large, clinical trial involving nearly 1,800
U.S. military veterans with type 2 diabetes—the most common form of
diabetes—provides further evidence that tight blood glucose control may
indeed protect the cardiovascular system. Reporting in The New England Journal of Medicine ,
researchers found a significant reduction in a composite measure of
heart attacks, strokes, heart failure, and circulation-related
amputations among the vets who maintained tight glucose control for
about five and a half years on average. What’s particularly encouraging
is most of the cardiovascular-protective benefit appears to be
achievable through relatively modest, rather than super strict,
reductions in blood glucose levels.
To assess blood glucose control, the
Veterans Affairs Diabetes Trial (VADT) used a common laboratory blood
test for glycosylated hemoglobin A1C, often simply referred to as A1C.
This test, which measures the amount of glucose attached to hemoglobin
in red blood cells, reflects a person’s average blood glucose level over
the preceding two to three months. A normal A1C level is below 5.7
percent, while levels between 5.7 and 6.4 percent indicate an increased
risk of diabetes. People with frank diabetes usually have A1C levels
above 6.5 percent.
When they enrolled in the VADT study, all of the veterans had
long-standing type 2 diabetes; had cardiovascular disease or were at
high risk for cardiovascular disease; and had poorly controlled blood
glucose levels (their A1C readings averaged 9.4 percent). Half were
assigned to an intensive therapy regimen, while the others remained on
standard treatment for an average of 5.6 years.
The primary difference between the two treatment approaches were the
doses of glucose-lowering oral medications (metformin, rosiglitazone,
and/or glimepiride) and when insulin therapy was initiated. Patients in
the intensive therapy group were prescribed doses of oral medication
that were twice as high as standard. In addition, they received insulin
when their A1C levels rose above 6 percent, compared to 9 percent for
the standard therapy group. All participants also received aspirin and a
cholesterol-lowering statin drug to control other cardiovascular risk
During the clinical trial, the vets in the intensive therapy group
lowered their A1C levels to 6.9 percent on average, compared to 8.4
percent in the standard care group—a significant difference. However,
follow-up work, led by Rodney Hayward at the University of Michigan and
the Ann Arbor VA Healthcare System, found that the effect did not
persist: three years after the trial ended, both groups’ A1C levels
hovered around 8 percent, separated by just 0.2 to 0.3 percentage
Still, nearly 10 years after the vets signed up for VADT, those who
received intensive therapy were 17 percent less likely to suffer major
cardiovascular events than their standard therapy counterparts. However,
no differences were seen in cardiovascular-related deaths. According to
the researchers, this may be partially due to recent life-saving
improvements in the way the public, emergency personnel, and health-care
professionals respond to heart attacks and strokes.
When the VADT results are considered along with those from three
previous major clinical trials of blood glucose control, the researchers
say the data underscore the importance of encouraging everyone with
diabetes to strive for at least a moderate level of blood glucose
control. They concluded that an average long-term A1C level of 8 percent
was sufficient to reap most of the cardiovascular benefits. While a 7
percent A1C level can be safely attained in many people, the intense
therapy needed to maintain such tight blood glucose control may not
always be worth it in terms of cardiovascular protection.
One thing is clear: the number of Americans with type 2 diabetes
continues to rise, and more research is needed into this major public
health challenge. For example, the VADT study included only 47 females,
so further work is needed to confirm its findings in larger groups of
women with type 2 diabetes. Hayward and his colleagues also plan to
continue to follow the VADT participants to see whether the
cardiovascular benefits of better blood glucose control hold up over
Another important take-home message is that each individual with
diabetes needs to work closely with his or her physician to weigh the
benefits and risks of tight blood glucose control and develop a
personalized diabetes management plan that takes into account
cardiovascular risk, age, and a variety of other factors. Keep in mind
that very low blood glucose levels (hypoglycemia) from too much insulin
can also cause serious health problems, including fainting, seizures,
and even death.
The new Precision Medicine Initiative stands ready to provide some
help in this area. In a population of 1 million American volunteer
participants, there will be tens of thousands of people with type 2
diabetes. This will provide an unprecedented opportunity to test new
methods of disease management. Currently, most people with diabetes have
to rely on a regular routine of finger pricks, test strips, and
hand-held monitors to track their blood glucose levels between A1C lab
tests. Among the many goals of the Precision Medicine Initiative is to
support research aimed at developing and testing ways of gathering such
biological data in real-time using a variety of innovative wireless
technologies. In the case of blood glucose, researchers are already
exploring ideas ranging from a needle-free “tattoo” that uses a mild
electrical current to measure glucose levels in the skin to a “smart”
contact lens that gets its glucose readings from a person’s tears.
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