Patients with Very Low Glucose Have Slightly Higher Risk of Death
blood sugar level lowers risk of heart attack, amputation, kidney
April 18, 2011 - A new study
of older diabetes patients has found that well-controlled blood sugar
levels were associated with a lower risk of major complications such as
heart attacks, amputation and kidney disease, but the very lowest blood
sugar levels were associated with a small but significant increased risk
The study published in the
June 2011 issue of the journal Diabetes Care, followed more than 70,000
type 2 diabetes patients, over 60 years of age, from Kaiser Permanente
for four years.
Because these findings come
from an observational study and not a randomized clinical trial, more
research needs to be done to fully understand their clinical
"We saw increased mortality
and complications, as anticipated, among those with very high blood
sugars, but we also saw a modestly increased risk of death among those
with very low levels of blood sugar," said the study's lead author
Elbert Huang, MD, associate professor of medicine at the University of
Researchers indicated that the
best overall outcomes were found among those with intermediate levels of
Huang and Andrew Karter, PhD,
from Kaiser Permanente Division of Research in Oakland, CA, jointly lead
the Diabetes & Aging Study, the largest observational study to assess
diabetes in older adults in the United States. The 5-year, National
Institutes of Health-funded study investigates care and health outcomes
in older patients with type 2 diabetes in a typical community setting.
Most current guidelines
suggest keeping glucose levels for patients with diabetes quite low. For
people without diabetes, the normal glucose level - measured by a test
called hemoglobin A1C, which reflects the average blood glucose level
over the previous three months - is between 4 percent and 6 percent,
compared to 6 and higher for patients with diabetes.
Because higher levels are
associated with complications from this chronic disease, most
recommendations for people with diabetes suggest maintaining an A1C less
than 7 percent
Concerns about current
"We need more evidence
regarding how well the 7-percent guideline, which was based on a 1998
British trial that excluded older patients, applies to patients over the
age of 60," said study co-author Andrew J. Karter, PhD, and the study's
principal investigator at the Kaiser Permanente Division of Research.
Recent studies have raised
concerns. In 2008, the Action to Control Cardiovascular Risk in Diabetes
(ACCORD) trial was halted after it showed a higher rate of mortality in
older patients who received very intensive glucose-lowering treatments.
"In our study," said Huang,
"we found the best overall outcomes among those with the intermediate
levels of control, those with A1Cs below 8 percent but above 6 percent.
We observed similar patterns for those in their 60s, 70s, and over 80."
Finding the optimal A1C target
is a balancing act, the authors note. The risk of all complications rose
with blood sugar levels, but those with an A1C between 6 and 8 percent
had the lowest death rates. While those with very poorly controlled
blood sugars—A1C over 10 percent—had the highest rates of death, those
with an A1C below 6 were also at a somewhat higher than those with an
A1C between 6 and 8 percent.
"We cannot say whether this
unexpected finding is due to the very low blood sugar itself, the
treatments used to control blood sugars, or to some other factors not
directly related to the care of diabetes," Karter explained. "It may be
that the sickest patients at high risk of dying simply had low blood
sugars to start with, rather than anything directly associated with the
care of diabetes increasing the risk of death."
"Further research, he added,
"will be focused on identifying the mechanisms that underlie the
somewhat increased mortality among those with very low A1C."
Since 1993, researchers
involved in the Kaiser Permanente Northern California Diabetes Registry
report having collected extensive epidemiological data on diabetes care
and observed health outcomes. The Diabetes & Aging Study follows
patients managed by Kaiser physicians using internal care guidelines
that mirror national clinical practice. Patients achieve varying levels
of blood sugar control. Such community-based studies complement clinical
trials by measuring whether the benefits of treatments measured in an
experimental setting are also observed in usual practice settings.
The National Institute of
Diabetes, Digestive and Kidney Diseases supported the research.
Additional authors include Jennifer Y. Liu, MPH and Howard H. Moffet,
MPH, Division of Research, Kaiser Permanente Northern California; and
Priya M John, MPH, Section of General Internal Medicine, University of
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