Linear Loss of Insulin Secretory Capacity During the Last Six Months Preceding IDDM: No effect of antiedematous therapy with ketotifen
- Kirsten P Böhmer, MD,
- Hubert Kolb, PHD,
- Bernd Kuglin, MD,
- Jürgen Zielasek, MD,
- Achim Hübinger, MD,
- Eberhard F Lampeter, MD,
- Bruno Weber, MD,
- Victoria Kolb-Bachofen, PHD,
- H U Jastram, MD,
- Jörg Bertrams, MD and
- F Arnold Gries, MD
- Diabetes Research Institute at the University of Düsseldorf Düsseldorf
- Department of Pediatrics, University of Berlin Berlin
- Department of Pediatrics, City Hospital Kaiserslautern
- Elisabeth Hospital Essen
- Institute for Immuno-biology, University of Düsseldorf Düsseldorf, Germany
- Address correspondence and reprint requests to Kirsten P. Böhmer, MD, Diabetes Research Institute at the University of Düsseldorf, Aufm Hennekamp 65, 40225 Düsseldorf, Germany.
Abstract
OBJECTIVE To investigate the effect of an antiedematous therapy with the histamine antagonist ketotifen on β-cell function in late prediabetes.
RESEARCH DESIGN AND METHODS In a randomized double-blind placebo-controlled study, ketotifen was administered for 3 months to 9 islet cell antibody positive (ICA+) prediabetic patients with a first-phase insulin response (FPIR) below the 2.5th percentile to preserve residual β-cell function. Patients were followed by intravenous glucose tolerance tests (IVGTTs) every 4—6 weeks for determination of FPIR, HbA1, ICAs, and insulin autoantibodies. In 5 patients, the immune activation state was followed by determination of serum levels of tumor necrosis factor-α (TNF-α), (β2-microglobulin, and C-reactive protein (CRP).
RESULTS Seven of nine patients developed diabetes within one year of followup. Irrespective of treatment with ketotifen, a slow and linear decline (P < 0.05) of 1 + 3-min insulin values was observed in sequential IVGTTs in those 7 patients who developed insulin-dependent diabetes mellitus (IDDM) during follow-up. The 2 other patients showed wide fluctuations of the insulin response with a threefold increase of initial insulin levels. HbAi did not correlate with FPIR. Fasting blood glucose increased significantly during the study (P < 0.05). Individual levels of serum TNF-α, CRP, and β2-microglobulin did not change during the study.
CONCLUSIONS The study could not demonstrate preservation of β-cell function by ketotifen in the late stage before manifestation of clinical diabetes. Manifestation is preceded in the last 6 months by a steady loss of the FPIR without rapid deterioration immediately before diagnosis and without signs of increased immune activity.
- Received November 10, 1992.
- Accepted August 7, 1993.
- Copyright © 1994 by the American Diabetes Association
