Linear loss of insulin secretory capacity during the last six 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 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.
Böhmer
K P
KP
Diabetes Research Institute, University of Düsseldorf, Germany.
Kolb
H
H
Kuglin
B
B
Zielasek
J
J
Hübinger
A
A
Lampeter
E F
EF
Weber
B
B
Kolb-Bachofen
V
V
Jastram
H U
HU
Bertrams
J
J
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
D001323:Autoantibodies; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D007665:Ketotifen; C024211:islet cell antibody