Zusammenfassung
Die Frage, ob eine alleinige Blutzuckersenkung die kardiovaskuläre
Ereignisrate bei langjährigen Typ 2 Diabetikern beeinflussen
kann, wird nach wie vor kontrovers diskutiert. Neue Erkenntnisse liefern
die Studien ACCORD, ADVANCE, VADT und die UKPDS-Nachbeobachtung.
Die drei erstgenannten Untersuchungen machen deutlich, dass mikrovaskulärer
und makrovaskulärer Benefit einer strengen BZ-Kontrolle
getrennt beurteilt werden müssen: Während der
günstige Einfluss auf mikrovaskuläre Komplikationen
wie die diabetische Nephropathie unstrittig ist, bleibt der generelle
makrovaskuläre Nutzen in diesen Megastudien weiterhin fraglich
und muss im Zusammenhang mit dem individuellen globalen Risiko betrachtet
werden. Demgegenüber konnten die Langzeitergebnisse der
Diabetesinterventionsstudie DIS und die UKPDS-Nachbeobachtung zeigen,
dass eine frühzeitige intensivierte BZ-Einstellung das
kardiovaskuläre Outcome durchaus nachhaltig positiv verändert – der
Einfluss kommt aber erst nach einem relativ langen Zeitraum von
ein bis zwei Jahrzehnten zum Tragen. Erstmalig wurde in der PROactive-Studie
der kardiovaskuläre Nutzen einer antidiabetischen Einzelsubstanz
(Pioglitazon) beim fortgeschrittenen Diabetes mit multiplen Manifestationen
einer Makroangiopathie nachgewiesen. Hier zeigte sich bereits nach
knapp 3 Jahren ein makrovaskulärer Benefit. Allerdings
stellte sich dieser nicht primär als Resultat der Blutzuckersenkung
dar, sondern als therapeutischer Nutzeffekt der komplexen Wirkungen
des PPARγ-Agonisten Pioglitazon auf Insulinresistenz, Lipoproteinspektrum,
Blutdruck, Endothelfunktion und auf Biomarker der subklinischen
Entzündung. Dies macht deutlich, dass wir pleiotrope Effekte
antidiabetischer Substanzen auf das metabolische Syndrom und die
Auswirkungen auf kardiovaskuläre Endpunkte stärker
in Therapieentscheidungen einbeziehen sollten. Für diese
komplexen Fragestellungen wird eine breite wissenschaftliche Evidenz
in Form von Endpunktstudien angestrebt, die für die allermeisten
Antidiabetika bisher jedoch nicht verfügbar ist.
Abstract
It is still a much debated question whether antidiabetic therapy to
target normal glycated hemoglobin levels would reduce cardiovascular
events in patients with advanced type 2 diabetes. New findings result
from ACCORD, ADVANCE and VADT. These trials reveal that microvascular
and macrovascular effects of intensive glucose lowering have to
be considered separately: Glycemic control convincingly demonstrated
to have a protective impact on microvascular complications, especially
nephropathy. However, macrovascular benefits remain doubtful in
these megatrials and have to be considered in connection with the
individual global risk. On the other hand, the Diabetes Intervention
Study (DIS) and UKPDS 10-year follow-up results yielded better cardiovascular
outcomes for those patients who received intensive glucose-lowering
therapy very early after diabetes diagnosis, but the favourable
influences did not manifest until a time period of 1 – 2
decades. For the first time, the cardiovascular benefit of an antidiabetic
substance (pioglitazone) could be verified in the large-scale outcome-trial
PROactive for patients with advanced diabetes and multiple manifestations
of macroangiopathy. The results provide strong support for a beneficial influence
on macrovascular complications just under 3 years of treatment.
Nevertheless, the positive findings did not result from better glycemic
control, but from the complexity of effects of PPARγ agonist
pioglitazone on insulin resistance, lipoprotein spectrum, blood
pressure, endothelial function and biomarkers of subclinical inflammation.
It is obvious that we need to integrate such pleiotropic effects
on metabolic syndrome and cardiovascular disease to improve the
quality of drug-therapy decisions. This, in turn, requires a growing
body of evidence from large, long-term outcome trials – but
appropriate data are still unavailable for the vast majority of
antidiabetic drugs.
Schlüsselwörter
ACCORD - ADVANCE - VADT - UKPDS - DIS - DCCT - PROactive - RECORD - Blutzuckerkontrolle
Keywords
ACCORD - ADVANCE - VADT - UKPDS - DIS - DCCT - PROactive - RECORD - blood glucose control
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Prof. Dr. med. Markolf Hanefeld
Zentrum für Klinische Studien GWT-TUD
GmbH
Fiedlerstraße 34
01307 Dresden
Phone: 0351 44 00 580
Fax: 0351
44 00 581
Email: hanefeld@gwtonline-zks.de
