LINEAR LOSS OF INSULIN SECRETORY CAPACITY DURING THE LAST 6 MONTHS PRECEDING IDDM - NO EFFECT OF ANTIEDEMATOUS THERAPY WITH KETOTIFEN

OBJECTIVE - To investigate the effect of an antiedematous therapy with the histamine antagonist ketotifen on beta-cell function in late pred iabetes. RESEARCH DESIGN AND METHODS - in a randomized double-blind pl acebo-controlled study, ketotifen was administered for 3 months to 9 i slet cell antibody positive (ICA+) prediabetic patients with a first-p hase insulin response (FPIR) below the 2.5th percentile to preserve re sidual beta-cell function. Patients were followed by intravenous gluco se tolerance tests (IVGTTs) every 4-6 weeks for determination of FPIR, HbA1, ICAs, and insulin autoantibodies. In 5 patients, the immune act ivation state was followed by determination of serum levels of tumor n ecrosis factor-alpha (TNF-alpha), beta2-microglobulin, and C-reactive protein (CRP). RESULTS - Seven of nine patients developed diabetes wit hin one year of follow-up. Irrespective of treatment with ketotifen, a slow and linear decline (P < 0.05) of 1 + 3-min insulin values was ob served in sequential IVGTTs in those 7 patients who developed insulin- dependent diabetes mellitus (IDDM) during follow-up. The 2 other patie nts showed wide fluctuations of the insulin response with a threefold increase of initial insulin levels. HbA, did not correlate with FPIR. Fasting blood glucose increased significantly during the study (P < 0. 05). Individual levels of serum TNF-alpha, CRP, and beta2-microglobuli n did not change during the study. CONCLUSIONS - The study could not d emonstrate preservation of beta-cell function by ketotifen in the late stage before manifestation of clinical diabetes. Manifestation is pre ceded in the last 6 months by a steady loss of the FPIR without rapid deterioration immediately before diagnosis and without signs of increa sed immune activity.