Abstract. Blood mononuclear cells obtained from 17 newly diagnosed insulin-dependent diabetic (IDDM) patients treated with insulin for 5 –7 days were assessed for the number of spontaneous and pokeweed mitogen (PWM)-stimulated immunoglobulin-secreting cells in a reverse haemolytic plaque assay. The spontaneous in vitro immunoglobulin secretion was evanescent and decreased in individual patients within 1–4 months of insulin treatment. Compared to matched controls, 53% (9/17) of the IDDM patients had an elevated spontaneous secretion of immunoglobulin, 41% (7/17) for IgG, 35% (6/17) for IgM, and 35% (6/17) for IgA. The quantities of PWM-stimulated IgG, IgM, or IgA secreting cells in IDDM were comparable to the controls. The IDDM patients with spontaneous immunoglobulin secreting cells had higher fasting C-peptide levels compared to the patients with immunoglobulin-producing cells within the normal range ( P < 0.05). The average titre of islet cell cytoplasmic antibodies was 1:26 in (9 out of 9 were positive) patients with, compared to 1:1 in patients (4 out of 8 were positive) without spontaneous secretion ( P = 0.025). These results suggest that the clinical onset of IDDM is associated with a polyclonal B lymphocyte activation and that higher levels of fasting C-peptide islet cell antibodies are associated with this immunoregulatory abnormality.
Plasma levels of islet cell cytoplasmic and cytotoxic antibodies were determined in 10 children with insulin-dependent diabetes mellitus (IDDM) treated with plasmapheresis shortly after diagnosis, and in 9 children with IDDM treated by conventional means alone. Islet cell cytoplasmic antibody (ICA) titers were determined by indirect immunofluorescence using unfixed sections of human pancreas, and islet cell cytotoxic antibody levels were determined in a complement-dependent antibody-mediated cytotoxicity (C'AMC) assay using a human fetal cloned insulin-producing cell line (JHPI-1) as target. Before plasmapheresis, ICA was present in 7 out of 10 children and C'AMC was positive in 4. Four successive treatments with plasmapheresis did not consistently decrease plasma levels of ICA or C'AMC. ICA was present in 15 out of the total 19 children at diagnosis, and titers of ICA decreased in 12 out of 15 subjects by at least 1 degree of dilution (1:3) at 18-30 months follow-up, whether or not they had been treated with plasmapheresis; C'AMC was positive in 6 out of the 18 children at diagnosis and decreased in 2 out of 6. Plasma levels of C-peptide did not differ at diagnosis but remained higher in the plasmapheresis treated diabetic children at 3 and 18-30 months follow-up. Neither ICA titers nor C'AMC levels correlated with plasma C-peptide responses at 18-30 months. It is concluded that plasmapheresis decreases ICA and C'AMC but is followed rapidly by a rebound effect, and does not affect the rates at which these islet cell antibodies decrease with increasing duration of IDDM.
SUMMARY We assessed HLA‐DR types and investigated serum samples for islet‐cell cytoplasmic antibodies (ICA) in 31 Danish patients with chronic pancreatitis. The antigen frequencies were compared with those in 1177 unrelated healthy Danish controls. Twenty patients had insulin‐dependent diabetes and 11 had normal intravenous glucose tolerance. No significant differences in the frequencies of DR3, DR4, or DR2 were found between patients with insulin‐dependent diabetes and patients with normal glucose tolerance or between any of these groups and controls. ICA were negative in all patients with chronic pancreatitis. It is concluded that the beta‐cell dysfunction in insulin‐dependent diabetes in chronic pancreatitis differs from that of classical insulin‐dependent diabetes.
The incidence of IDDM in the age group over 30 years was estimated in a historical prospective study, using clinical and biochemical measurements at onset as criteria for classification. The study population, nearly one million, represents 20% of the Danish population. The degree of ascertainment was >99%. One thousand two hundred and forty patients were treated with insulin during the study period (1973–77). Based on the clinical and biochemical variables, the patients were classified into three groups: insulin‐dependent diabetes mellitus (IDDM) accounted for 16.2%, insulin‐treated diabetes mellitus for 54.1% and short‐term treated diabetes mellitus for 29.6% of the total insulin‐treated group. The incidence of IDDM in the age group over 30 years at onset was 8.2 100 000 −1 year −1 . The cumulative incidence rate (0–90 years) was 1.5–1.6 per cent. The present study indicates that IDDM may develop at any age. Thus the life‐time risk of developing IDDM is higher than hitherto expected.
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