title: Linear loss of insulin secretory capacity during the last six months preceding IDDM. No effect of antiedematous therapy with ketotifen.
abstract: OBJECTIVE
  To investigate the effect of an antiedematous therapy with the histamine antagonist ketotifen on beta-cell function in late prediabetes.
  
  
  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 beta-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-alpha (TNF-alpha), beta 2-microglobulin, and C-reactive protein (CRP).
  
  
  RESULTS
  Seven of nine patients developed diabetes within 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 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. HbA1 did not correlate with FPIR. Fasting blood glucose increased significantly during the study (P < 0.05). Individual levels of serum TNF-alpha, CRP, and beta 2-microglobulin did not change during the study.
  
  
  CONCLUSIONS
  The study could not demonstrate preservation of beta-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.
authors.affiliation: Diabetes Research Institute, University of Düsseldorf, Germany.
authors.forename: K P
authors.initials: KP
authors.lastname: Böhmer
authors.forename: H
authors.initials: H
authors.lastname: Kolb
authors.forename: B
authors.initials: B
authors.lastname: Kuglin
authors.forename: J
authors.initials: J
authors.lastname: Zielasek
authors.forename: A
authors.initials: A
authors.lastname: Hübinger
authors.forename: E F
authors.initials: EF
authors.lastname: Lampeter
authors.forename: B
authors.initials: B
authors.lastname: Weber
authors.forename: V
authors.initials: V
authors.lastname: Kolb-Bachofen
authors.forename: H U
authors.initials: HU
authors.lastname: Jastram
authors.forename: J
authors.initials: J
authors.lastname: Bertrams
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000276:immunology; D007665:Ketotifen / Q000627:therapeutic use*; D008297:Male; D011236:Prediabetic State / Q000097:blood* / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D007665:Ketotifen; C024211:islet cell antibody