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Steroid amelioration of immunogenic insulin-resistant diabetes: a proposed mechanism.

Yale Journal of Biology and Medicine
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  • Research Article
  • Medicine


FRED S. KANTOR* Department of Internal Medicine, Yale PETER M. BERKMAN** University School of Medicine STEROID AMELIORATION OF IMMUNOGENIC INSULIN-RESISTANT DIABETES: A PROPOSED MECHANISMt Among the possible mechanisms of insulin resistant diabetes, binding of insulin in the intravascular' or interstitial compartments by antibody has received- considerable investigative attention.' Although adrenal steroid.s are often helpful in this situation,'evidence that steroid-induced reduction of insulin antibody is the cause of reduction in insulin requirement remains equivocal.2"3 Two observations suggest that amelioration of insulin resistance is not caused by steroid-induced suppression of antibody formation: (a) insulin requirement often falls quickly, within the first week of treatment, whereas the half life of gamma globulin is two weeks or more; and (b) the measured reduction in insulin antibodies does not correspond well to the change in insulin requirements.2 The present report was stimulated by the admission to Yale-New Haven H-ospital of a 72-year-old Negro woman in diabetic acidosis, who. required 3,200 units of insulin (Lilly)t to achieve a precarious control of carbo- hydrate metabolism. After the initial episode, maintenance of' diabetic control necessitated 350-400 units of insulin daily. On three. separate occasions this requirement fell to 80-100 units daily within six days after institution of steroid therapy. Evidence is presented in this report to demonstrate that: (a) insulin binding was predominately, but not exclu- sively, by. gamma G globulin; (b) steroi.d treatment did not affect.the half life of circulating insulin-anti insulin complexes; (c) serum obtained prior to steroid treatment consistently bound more insulin than did serum obtained after treatment when compared directly in equilibrium dialyses. MATERIALS AND METHODS Serum was obtained at the times specified and tested for its capacity to bind insulin by the method of Berson, et al.' using Il"l labelled beef insulin w

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