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The effect of a combined therapy with buformin and dichloroacetate on blood lactate concentrations in diabetics

Der Einfluß einer Kombinationsbehandlung mit Buformin und Dichlorazetat auf die Blutlaktatspiegel bei Diabetikern

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Zusammenfassung

Im Tierversuch vermag Dichlorazetat (DCA), das die Pyruvatdehydrogenase stimuliert, erhöhte Blutlaktatspiegel unter Biguaniden zu senken. Bei 10 Erwachsenendiabetikern wurde daher der Einfluß einer Kombinationsbehandlung mit Buformin und DCA (400 mg tgl.) auf die Blutlaktatspiegel untersucht und mit einer analogen Vor- und Nachperiode einer alleinigen Buforminbehandlung (200 mg tgl.) über 6 Tage verglichen. Die Diabeteseinstellung blieb gemessen an den mittleren Blutglucosekonzentrationen während der 3 Untersuchungsperioden unverändert. Ebenfalls keine signifikanten Unterschiede, weder nüchtern noch postprandial, ergaben sich hinsichtlich der Laktat-und Ketonkörperspiegel im Blut. Im Anschluß an einen standardisierten Ergometertest jedoch stieg unter der Kombinationstherapie mit Buformin und DCA das Blutlaktat wesentlich geringer an (p<0,05) als unter Buformin allein. Gleichzeitig wurden unter der Kombinationstherapie weniger Ketonkörper vom arbeitenden Muskel utilisiert (p<0,05). Diese Ergebnisse stimmen mit Tierversuchen gut überein und können im Sinne einer vermehrten Pyruvatoxidation unter DCA interpretiert werden; es ist zu hoffen, daß DCA ähnlich wie beim Tier auch bei biguanidbehandelten Diabetikern einem excessiven Ansteigen der Blutlaktatspiegel vorbeugen kann.

Summary

In animals, dichloroacetate (DCA) which activates pyruvate dehydrogenase has been shown to diminish increased blood lactate concentrations due to biguanide treatment. In 10 maturity onset diabetics, therefore, the effect of a combined therapy with buformin and DCA (200 mg b.i.d.) was studied on blood lactate concentrations and compared with an analogous pre- and postinvestigation period of 6 days with buformin treatment alone (100 mg b.i.d.). Mean blood glucose concentrations remained the same during all 3 investigation periods. Also, neither fasting nor postprandially significant differences were found in blood lactate and ketones. In association with a standardized ergometer test, however, the rise in blood lactate was significantly smaller (p<0.05) while the patients were on buformin plus DCA, compared to the periods when only buformin was given. Furthermore, less ketone bodies appeared to be utilized by the exercising muscle under the influence of the combined treatment (p<0.05). These results are in good agreement with animal studies and suggest that DCA might be as effective in decreasing enhanced blood lactate concentrations in biguanide treated man as in animals.

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  1. Forschergruppe Diabetes und III. Medizinische Abteilung, Schwabinger Krankenhaus München, Germany

    E. Standl, H. -U. Janka, A. Standl, M. Haslbeck & H. Mehnert

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  1. E. Standl
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  2. H. -U. Janka
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  3. A. Standl
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  4. M. Haslbeck
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  5. H. Mehnert
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Standl, E., Janka, H.U., Standl, A. et al. The effect of a combined therapy with buformin and dichloroacetate on blood lactate concentrations in diabetics. Klin Wochenschr 55, 969–971 (1977). https://doi.org/10.1007/BF01479229

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  • DOI: https://doi.org/10.1007/BF01479229

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