Jörg Bertrams

Elevated Levels of Circulating Adhesion Molecules in IDDM Patients and in Subjects at Risk for IDDM

Serum levels of recently discovered circulating forms of adhesion molecules, ICAM-1 and L-selectin, were found to be elevated in IDDM patients and in subjects at risk for developing IDDM compared with 100 normal, nondiabetic blood donors. Both adhesion molecules were determined by sandwich ELISA. Serum concentrations of either clCAM-1 or cL-selectin were >2SD of normal mean in 10 of 14 recent-onset IDDM patients (P < 0.05). Serum levels of clCAM-1 and cL-selectin did not correlate. In first-degree relatives, elevated adhesion molecule levels were observed in the 6 ICA+ individuals and in the ICA− individuals all (n = 14) with a genetic risk of IDDM (sharing HLA-DR3 and/or -DR4− with the diabetic relative) but not in the HLA-DR3− and/or -DR4− relatives (n = 13). We conclude that elevated clCAM-1 and cL-selectin levels occur independently of ICA status and probably reflect ongoing immune processes in recent-onset IDDM patients and first-degree relatives at risk for IDDM.

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 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.

Proinsulin autoantibodies: association with type I diabetes but not with islet cell antibodies, insulin autoantibodies or HLA-DR type.

Antibodies reacting with proinsulin but not with insulin determinants have been observed recently in Type I diabetes. We describe here that ELISA-determined proinsulin autoantibodies (IgG-PAA) also occur in first-degree relatives of IDDM patients (38/513, 7.4% vs 1.9% in controls, P less than 0.025). In contrast to insulin autoantibodies (IgG-IAA) and islet cell antibodies (ICA) no association with HLA type was found. Furthermore, IgG-PAA occur independently of IgG-IAA and ICA. We conclude that the humoral autoimmune response to proinsulin determinants is under separate genetic control.

Genetic analysis workshop IV: Insulin dependent diabetes mellitus ‐ summary

The Insulin Dependent Diabetes Mellitus (IDDM) study was one of the topics of Genetic Analysis Workshop IV (GAW IV) discussed October 7 - 8 at a pre-workshop meeting and presented October 9, 1985 at the American Society of Human Genetics meeting in Salt Lake City. The aim of the study was to have different groups analyze an identical body of real data in order to compare their analytical methods and the results based on their different approaches. This summary describes the available datasets and presents the main results of the nine participating groups. The detailed descriptions of analytical methods and results are presented in the individual papers following this overview. Although differing analytical methods were used there were no discrepancies regarding the interpretation of the data. Whereas the presented gametic associations were well established before, the real gain of this workshop was the unanimous result that the recessive 2-allele-model with incomplete penetrance had to be rejected and at least a 3-allele-model with differing susceptibility alleles and differing penetrances for heterozygotes and homozygotes had to be postulated for the transmission of IDDM.

A new partially deficient variant in the phosphoglucomutase 1 system, PGM1*W31

SummaryIn a case of disputed paternity an inherited hyposynthetical variant of the PGM1*1A gene was identified. This variant could not be detected by conventional electrophoresis on cellulose acetate membranes but clearly appeared on polyacrylamide gels after isoelectric focusing. The enzyme activity of this variant was about 25% of the normal PGM1*1A protein. The variant was designated PGM1*W31.