Millions of pre-diabetic Americans may be at
increased risk of future stroke, say researchers at the University of
California, San Diego School of Medicine in a new meta-analysis of
epidemiological studies, but the precise degree of that threat is confounded by
differing medical definitions and factors that remain unknown or unmeasured.
"The
immediate implication of our findings is that people with pre-diabetes should
be aware they are at increased risk of stroke, and that this condition is
frequently associated with one or more major risk factors for
cardiovascular disease," said Bruce Ovbiagele, MD, a professor of
neurosciences at UC San Diego School of Medicine and the study's senior author.
"Beyond that, there's a great need to further refine our understanding of
that risk and how it's measured."
Writing
in the June 8 online edition of the British Medical
Journal, Ovbiagele and an international team of colleagues reviewed 15
qualifying prospective cohort studies that looked at the association between
pre-diabetes and stroke risk. The studies, published between 2004 and 2011,
involved 760,925 participants.
Pre-diabetes
occurs when blood glucose
levels are consistently higher than normal, but not yet high enough to
be diagnosed as diabetes. The condition is widespread in the United States: An
estimated 35 percent of American adults – approximately 79 million people – are
believed to be pre-diabetic, and thus at greater risk of developing full-blown
type-2 diabetes, which afflicts roughly 26 million Americans.
Diabetes
is the seventh leading cause of death in the U.S., and a major risk factor for
heart disease and stroke, the first and fourth leading causes of death.
People
with pre-diabetes typically have the same risk factors for cardiovascular
disease as people with type 2 diabetes – specifically, high blood pressure,
high cholesterol levels and obesity – but the condition's effect on future
stroke risk has not been established.
Ovbiagele
and colleagues found that an association between future stroke risk and
pre-diabetes depended upon the definition of the latter. To determine whether
someone has pre-diabetes, blood glucose levels are
typically measured after a 12-hour fast. According to the 1997 American
Diabetes Association (ADA), a normal fasting glucose measurement ranges between
70.2 to 100 milligrams per deciliter (mg/dL). A level between 100 and 126 mg/dL
is considered pre-diabetic. A level of 126 mg/dL or above is diabetic.
By the
1997 standard, the researchers found that pre-diabetics in the studies with a
fasting glucose measurement of 110 to 125 mg/dL carried a 21 percent higher
chance of suffering a future stroke. Heart disease and stroke account for
roughly two-thirds of all deaths among people with diabetes.
In
2003, however, the ADA redefined the fasting glucose level for pre-diabetes to
100 to 125 mg/dL. Using this less stringent definition, the researchers found
no increased stroke risk for pre-diabetics. Indeed, when they analyzed three
studies that provided information on participants with fasting glucose levels
of 100 to 109 mg/dL they found no increased risk of
stroke.
Ovbiagele
said the difference in the findings suggests there may be a "threshold
effect" in the relationship between fasting glucose levels and future
stroke risk. "Elevated risk may only begin at or above a fasting glucose level
of 110 mg/dL," he said.
Additional
research is needed to determine the best definition predicting stroke risk
among diabetics, Ovbiagele noted. It should include an assessment of more
recent glycemic biomarkers, such as glycosylated hemoglobin, and be followed by
randomized, controlled trials involving drugs and/or lifestyle modification to
evaluate the effect of treatments on reducing the risk of future strokes.
"In
the meantime, to avoid progression to diabetes or occurrence
of strokes, clinicians should strongly consider recommending therapeutic
lifestyle changes and maximizing the control of established stroke risk factors
in their patients with pre-diabetes," Ovbiagele said.
Provided
by University
of California - San Diego
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