Behandlung
der Zuckerkrankheit (Diabetes mellitus): auch
ein zu niedriger HbA1c-Wert
erhöht beim Diabetiker das Sterberisiko.
Es
ist schon lange bekannt, dass ein auf Dauer erhöhter
Blutzuckerspiegel bei Diabetikern mit einem ebenso
erhöhten Risiko für Herz-Kreislauf-Erkrankungen
verbunden ist. Dies führt bei schlecht eingestellten
Diabeteikern zu einem deutlich erhöhten Sterberisiko.
Jetzt
zeigt eine in Großbrittanien durchgeführte und im
Fachblatt
The Lancet publizierte Studie,
dass gleiches auch für Patienten gilt, deren Blutzuckerspiegel
aufgrund einer intensiven Behandlung zu niedrig
ist. Der Laborwert an dem sich Patienten und Ärzte
derzeit orientieren ist das
HbA1c.
(Hier
finden Sie Informationen zu diesem Wert)
Bisher
gingen die Ärzte davon aus, dass ein HbA1c
von
unter 6.5% erstrebenswert sei. Doch nun konnten
die Forscher von der Universität Cardiff nachweisen,
dass eine untere Grenze offenbar ebenso wenig unterschritten
werden sollte, wie eine obere. Ausserdem konnte
in der Untersuchung gezeigt werden, dass es nicht
unbedingt eine gute Idee ist einen Altersdiabtes
(Diabetes Typ 2 ) mit Insulin zu behandeln.
Diese
intensive Therapie scheint nämlich mit einem um
nahezu 50% erhöhten Sterberisiko behaftet zu sein.
In
einem begleitenden Kommentar kamen französische
Kardiologen zu dem Schluss, dass
ein HbA1c-Wert von 7·5% angestrebt werden
sollte.
Dieser Wert ist aus der Sicht des Statistikers mit
dem geringsten Herz-Kreislaufkomplikationen und
dem niedrigsten Sterberisiko verbunden.
THE LANCET: Press Release
INTENSIVE GLUCOSE CONTROL FOR DIABETES CAN LOWER
BLOOD GLUCOSE TOO FAR (HYPOGLYCAEMIA), AND INCREASE
MORTALITY RISK
Uncontrolled high blood glucose
(hyperglycaemia) in patients with diabetes is known
to increase mortality. But new research shows
that intensive treatment to
control blood glucose can lower it too far (hypoglycaemia),
which also increases mortality.
Thus blood glucose level targets should have lower
as well as upper limits, to lower the risk to patients.
Furthermore, patients
with type 2 diabetes given insulin-based regimens
have a 50% increased mortality risk compared to
those given combination oral therapy.
The findings are reported in an
Article
Online
First
(www.thelancet.com)
and in an upcoming edition of
The Lancet—written
by Dr Craig Currie, School of Medicine, Cardiff
University, UK, and colleagues.
The
specific goal for control of blood sugar is to return
glycated haemoglobin (HbA1c)*
to a normal range, because good blood sugar (glycaemic)
control is known to reduce risk of long-term small
blood vessel complications in both type 1 and type
2 diabetes. Reports of potentially raised mortality
rates associated with intensive glycaemic control
have triggered discussion about recommendations
for treatment of type 2 diabetes, specifically relating
to the optimum target for HbA1c.
Researchers
have suggested that hypoglycaemia contributes to
a heightened risk of mortality in patients with
diabetes.
Because intensive glycaemic control increases risk
of hypoglycaemia with some drugs more than with
others, assessment of risks associated with the
different blood glucose-lowering regimens is important.
In this study, the authors assessed the association
between all-cause mortality and HbA1c
in patients with type 2 diabetes in a primary-care
setting, and established whether any evident association
was independent of the diabetes treatment regimen.
Two cohorts of patients aged
50 years and older with type 2 diabetes were generated
from the UK General Practice Research Database from
November 1986
to November 2008.
The researchers identified 27 965 patients whose
treatment had been intensified from oral monotherapy
to combination therapy with oral blood-glucose lowering
agents (metformin plus sulphonylurea), and 20 005
who had changed to regimens that included insulin.
Those with diabetes secondary to other causes were
excluded. All-cause
mortality was the primary outcome.
Age, sex, smoking status, cholesterol, cardiovascular
risk, and general morbidity were identified as important
confounding factors, and the data were subsequently
adjusted for these factors.
Using
the glycated haemoglobin (HbA1c)
level with the lowest mortality risk (7.5%) as a
reference point, the researchers found that for
the two combined cohorts, mortality
risk in the lowest HbA1c
decile (6·4%) was 52% higher, and in the highest
HbA1c
decile (10·6%) was 79% higher.
The typical HbA1c
target
for diabetes treatment is 7.0%.
Results showed a similar U-shaped curve for both
oral combination therapy and insulin therapy.
However, all-cause
mortality in people given insulin-based regimens
(2834 deaths) was 49% higher than those give combination
oral agents (2035 deaths).
The
authors say that while the data suggest that insulin
could increase the risk of death in type 2 diabetes,
differences in the baseline characteristics of the
insulin treated patients (older, more comorbidities,
longer duration of diabetes) could be one reason
behind this risk; they also point out a possible
link between use of insulin and cancer progression
that has been reported in a previous study. However,
the authors wish to make clear they are not suggesting
diabetes patients who are prescribed insulin should
stop taking their medication. They say: “Whether
intensification of glucose control with insulin
therapy alone further heightens risk of death in
patients with diabetes needs further investigation
and assessment of the
overall risk balance.”
They
conclude: “Low and high mean HbA1c
values were associated with increased all-cause
mortality and cardiac events. If confirmed, diabetes
guidelines might need revision to include a minimum
HbA1c
value.”
In an accompanying
Comment,
Dr Beverley Balkau
and Dr Dominique Simon, CESP Centre for Research
in Epidemiology and Population Health, Inserm, Villejuif,
France, say: “In patients with type 2 diabetes,
when using insulin secretagogues or insulin itself,
today’s study does provide a rationale for
an HbA1c threshold of 7·5%, corresponding to the
lowest death rate and lowest event rate for large-vessel
disease. Priority should be given to insulin sensitisers
for as long as possible in patients with type 2
diabetes, because these drugs allow a low HbA1c
to be targeted without any risk of hypoglycaemia.
More research is needed to establish HbA1c thresholds
and the combination of drugs to be recommended for
intensive treatment, with perhaps differing recommendations
according to the patient—intensive treatment
seems to be more beneficial for cardiovascular outcomes
for those who are younger than 60 years, with a
short duration of diabetes, and absence of microvascular
and macrovascular disease.”
Dr Craig Currie, School of
Medicine, Cardiff University, UK. E)
currie@cardiff.ac.uk
Dr
Beverley Balkau, CESP Centre
for Research in Epidemiology and Population Health,
Inserm, Villejuif, France. E)
beverley.balkau@inserm.fr
For full Article
and Comment, see:
http://press.thelancet.com/diabetessurvival.pdf
Note to editors: Glycated
haemoglobin is a form of haemoglobin used to identify
the average plasma glucose concentration over prolonged
periods of time.
The HbA1c
level is proportional to average blood glucose concentration
over the previous four weeks to three months.