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Neue Erkenntnisse in der Behandlung der chronischen Insulinresistenz und experimentelle Untersuchungen zu ihrer Genese

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Zusammenfassung

Es werden drei Patienten mit chronischer Insulinresistenz beschrieben, deren Diabetes mellitus trotz Insulindosen von über 300 E pro Tag nicht einstellbar war. Es bestanden keine weiteren Erkrankungen, die das Auftreten der Insulinresistenz hätten erklären können. Bei hohen Blutzuckerwerten zwischen 200 und 400 mg-% und höher und starker Glucosurie führte bei allen Patienten ein Therapieversuch mit Nebennierenrindenhormonen zu bedrohlicher Verschlechterung der Stoffwechsellage. Biguanide und Sulfonylharnstoffe konnten keine Besserung herbeiführen.

Die systematische intravenöse Verabreichung des Insulins bewirkte ein Verschwinden der Acetonurie und der subjektiven Beschwerden innerhalb von Stunden und eine Rückbildung der Glucosurie und einen Abfall der Blutzuckerwerte zur Norm innerhalb von 5–10 Tagen. Wurde die intravenöse Therapie langsam wieder durch subcutane Insulininjektionen ersetzt, zeigte sich, daß die Insulinresistenz bei zwei Patienten durchbrochen, bei dem dritten Patienten entscheidend gebessert war. Bei letzterem konnte die Insulinresistenz durch eine anschließende 10tägige Behandlung mit Nebennierenrindenhormon endgültig durchbrochen werden.

Eine insulinzerstörende Kraft sowie insulinbindende oder insulinneutralisierende Antikörper konnten bei keinem Patienten nachgewiesen werden. Die insulinähnliche Aktivität im Serum war in keinem Fall und in keinem Stadium erniedrigt, sondern entweder normal oder erhöht. Dem Serum in vitro zugefügtes Insulin wurde bei dem ersten Patienten quantitativ wiedergefunden. Im Hypoglykämieversuch an der Maus schützte das Patientenserum die Mäuse in keinem Fall gegen die tödliche Insulinhypoglykämie. Die Reaktionsfähigkeit des Fettgewebes des zweiten Patienten auf Insulin, gemessen an der Glucose-1-C14-Oxydation zu C14O2, war gegenüber normalem menschlichem Fettgewebe herabgesetzt.

Es wird die Vermutung geäußert, daß in diesen Fällen der Insulinresistenz ein vermindertes Ansprechen der peripheren Gewebe auf die Insulinwirkung zugrunde liegt. Der therapeutische Erfolg mit Nebennierenrindenhormon bei dem dritten Patienten spricht für eine immunbiologische Ursache, wobei möglicherweise sessile Antikörper eine Rolle spielen.

Nach unseren Erfahrungen ist die systematische intravenöse Insulintherapie bei der chronischen Insulinresistenz die Therapie der Wahl. Bedrohliche Dekompensationserscheinungen des Kohlenhydratstoffwechsels können mit Sicherheit durchbrochen werden. Wird die intravenöse Insulintherapie 5 bis 10 Tage fortgesetzt, kann die Insulinresistenz dauerhaft beseitigt werden.

Summary

Three patients with chronic insulin resistance are being described. Their diabetes mellitus, despite doses of insulin of more than 300 units per day, could not be regulated. There were no further diseases, which might have been able to explain the appearance of this insulin resistance. With high fasting blood sugar values of between 200 and 400 mg-% and higher and strong glycosuria a therapeutic attempt with adrenal cortical steroids on all patients led to a threatening deterioration of the situation in their actual carbohydrate metabolism. Biguanides and sulfonylureas were unable to bring about any improvement.

The systematic intravenous injection of insulin caused a disappearance of the acetonuria and of subjective complaints within hours and a backformation of the glycosuria and a decline of the fasting blood sugar values back to normal within five to ten days' time. When the intravenous therapy was again slowly replaced by subcutaneous insulin injections, it appeared that the insulin resistance had been brocken in the case of two patients, while it had, in the case of the third patient, decidedly improved. In the case of the latter the insulin resistance could be finally broken by a subsequent ten days' treatment with adrenal cortical steroids.

An insulin-destroying force as well as insulin-binding or insulin-neutralising antibodies could not be proved to exist in any of the patients. The insulin-like activity in the serum was in no case and in no phase lowered, but it was either normal or increased. Insulin added to the serum in vitro was in the case of the first patient quantitatively recovered. In the hypoglycemia test on the mouse, the patient's serum did in no case protect the mice from the fatal insulin hypoglycemia. The responsiveness of the adipose tissue of the second patient to insulin, measured by the glucose-1-C14-oxydation to C14O2, was lowered as compared with normal human adipose tissue.

The assumption is being expressed that in these cases of insulin resistance a lowered reaction of the peripheral tissue to the insulin effect is at the base. The therapeutical success with adrenal cortical steroids in the case of the third patient points in the direction of an immunbiological cause, whereby possibly sessile antibodies may play a part.

According to our experience, the systematic intravenous insulin therapy in the case of chronic insulin resistance is the therapy of choice. Threatening decompensation appearance of the carbohydrate metabolism can be broken with certainty. If the intravenous insulin therapy is being continued for five to ten days' time, the insulin resistance can be permanently removed.

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Authors and Affiliations

  1. Aus der II. Medizinischen Klinik und Poliklinik der Medizinischen Akademie Düsseldorf, Germany

    H. Daweke & I. Bach

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  1. H. Daweke
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Herrn Prof. Dr. med.K. Oberdisse zum 60. Geburtstag gewidmet.

Mit dankenswerter Unterstützung des Bundesministeriums für Atomkernenergie und Wasserwirtschaft.

Auszugsweise vorgetragen auf dem 1. Symposion des Deutschen Diabetes-Komitee, Düsseldorf. 26./27. 10. 62.

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Daweke, H., Bach, I. Neue Erkenntnisse in der Behandlung der chronischen Insulinresistenz und experimentelle Untersuchungen zu ihrer Genese. Klin Wochenschr 41, 257–264 (1963). https://doi.org/10.1007/BF01483389

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