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Aktuelle Neurologie 2006; 33(10): 543-552
DOI: 10.1055/s-2006-940077
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Peripher-neurogene Läsionen bei Diabetes mellitus

Peripheral Neurogenic Lesions in Diabetes MellitusS.  Haußleiter1 , M.  Tegenthoff1
  • 1Neurologische Universitätsklinik Ruhr-Universität Bochum BG-Kliniken Bergmannsheil
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Publikationsverlauf

Publikationsdatum:
25. September 2006 (online)

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Zusammenfassung

Polyneuropathien sind generalisierte Erkrankungen des peripheren Nervensystems. Der Diabetes mellitus ist die Hauptursache solcher Neuropathien, und die Neuropathie wiederum ist die häufigste diabetische Komplikation. Alle Diabetesformen sind gekennzeichnet durch eine chronische Hyperglykämie und die Entwicklung diabetesspezifischer mikrovaskulärer Veränderungen. Die Blutgefäße benötigen zur Funktionserhaltung eine angemessene neurale Regulation und die Nervenzellen entsprechend eine ausreichende kapilläre Ernährung. Die diabetische Neuropathie entsteht vermutlich sowohl direkt durch die schädlichen Auswirkungen der Hyperglykämie auf das Nervenparenchym, als auch indirekt durch die Veränderungen des neurovaskulären Blutflusses mit konsekutiver neuronaler Ischämie. Primäre Ursache und größter Risikofaktor für pathologische Veränderungen und klinische Komplikationen bei einem therapeutisch unzureichend eingestellten Diabetes mellitus ist die permanent existierende Hyperglykämie im Organismus. Die meisten Zellen reduzieren bei einem Überangebot an Glukose entsprechende Transportvorgänge nach intrazellulär. Renale, retinale und neuronale Zellen verfügen jedoch nicht über diesen Mechanismus und können daher nicht adäquat auf persistierende Hyperglykämien reagieren. Die Abhängigkeit pathologischer Auswirkungen vom intrazellulären Glukosespiegel legt nahe, dass sich ursächliche Mechanismen ebenfalls innerhalb der Zelle abspielen. Der Polyol- und Hexosaminpfad, eine vermehrte Glykosylierung, die Aktivierung der Proteinkinase C und oxidativer Stress scheinen hierbei wesentlich zu sein. Sie beschreiben einerseits direkte toxische Auswirkungen der Hyperglykämie und resultierender pathophysiologischer Konsequenzen (Oxidanzien, Hyperosmolarität, Glykosylierungsprodukte) auf das Gewebe, andererseits den Effekt veränderter Signalkaskaden (Phospholipide, Kinasen) durch die Produkte des Glukosestoffwechsels. Die hyperglykämie-induzierte vaskuläre Insuffizienz tritt beim Diabetiker bereits frühzeitig auf, entwickelt sich parallel zur progredienten neuronalen Dysfunktion und hält die schwerwiegenden strukturellen, funktionalen und klinischen Veränderungen der Erkrankung aufrecht.

Abstract

Polyneuropathy is a generalized disorder of the peripheral nervous system. Diabetes mellitus is the main cause of such neuropathies and neuropathy itself is the most frequent complication in diabetic patients. All forms of diabetes are characterized by hyperglycaemia and the development of specific micro-vascular alterations. Blood vessels consistently need neural regulation to maintain their function and nerve cells correspondingly require an appropriate nutrition through capillaries. The diabetic neuropathy probably results both directly from damaging hyperglycaemic effects on neural parenchyma, and indirectly from changes of the neurovascular blood flow with consecutive neuronal ischemia. Persisting hyperglycaemia of the organism is initiating cause and established risk factor for pathological changes and clinical complications in insufficiently treated diabetic patients. In case of hyperglycaemia most cells are able to reduce the transport into the cell. Some cells of retina, kidney and peripheral nerve lack this ability and therefore cannot compensate for ongoing hyperglycaemic states. Since pathological consequences depend on intracellular glucose levels, it seems reasonable that the underlying mechanisms take place inside the cell as well. Increasing flux through the polyol and hexosamine pathway, advanced glycosylation of molecules, activation of protein kinase C and finally oxidative stress seem to be of importance in this context. Those pathways describe toxic effects of the hyperglycemia and pathophysiological consequences on the tissue (oxidants, hyperosmolarity, advanced glycosylation end products), as well as the modification of signalling cascades by products of the glucose metabolism (phospholipids, kinases). Hyperglycaemically induced vascular insufficiency occurs early in diabetic patients, develops simultaneously to progressive neural dysfunction and maintains the severe structural, functional and clinical changes of the disease.

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Dr. Sibylle Haußleiter

Neurologische Universitätsklinik Ruhr-Universität Bochum · BG-Kliniken Bergmannsheil

Bürkle-de-la-Camp-Platz 1

44789 Bochum

eMail: ida@haussleiter.de