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Biomedical subjects

I Rjasanowski

Publications and source records attributed to I Rjasanowski.

48 records · Page 3Linked to original sources

The frequency of islet cell surface antibodies and antibody-dependent cell-mediated cytotoxicity (ADCC) of mononuclear cells in HLA-typed patients with high diabetes risk.

To evaluate the significance of ICSA as a prognostic marker for the development of type I diabetes we investigated 66 subjects with first degree relatives of type I (47) and type II (9) diabetes as well as subjects with anamnestical data suggestive of diabetes. Patients were studied for glucose tolerance (oGTT) and IRI-response, ICSA (indirect fluorescence of living rat islet cell suspensions), ADCC (specific 51Cr-release of serum pretreated neonatal rat islets elicited by mononuclear cells) and HLA-antigens. 23 subjects revealed normal glucose tolerance, 17 impaired glucose tolerance and 26 had a prevoius abnormality. The incidence of ICSA varied between 46 and 53 per cent, that of positive ADCC between 22 and 56 per cent, both being highest in subjects with IGT. 87 per cent of all patients revealed diabetes associated HLA-antigens. We found no correlation of ICSA with glucose tolerance, IRI-response, ADCC and HLA-antigens. In conclusion it can be said that ICSA are present in a high percentage in patients with high diabetes risk but their predictive role as a marker for the manifestation must be elucidated in follow-up studies.

Adolescent↗

Metabolic, hormonal, and immunological alterations in subjects with antecedent mumps infection.

Since mumps virus seems to be one of the most likely candidates in viral etiology of insulin-dependent diabetes (IDDM) we studied the possible relationship of glucose tolerance (75 g oGTT), beta cell function, diabetes associated HLA antigens, haptoglobin phenotype, islet cell antibodies (ICA) and islet cell surface antibodies (ICSA) in 125 subjects with antecedent mumps infection. Impaired glucose tolerance (IGT) was diagnosed in 3.2% (n = 4) but onset of diabetes did not appear within 14 months after mumps infection. There was no relationship between glucose tolerance and complications of antecedent mumps infection (e.g. pancreatitis, meningitis, orchitis). The prevalence rate of ICA was 76%. ICSA were detectable in about 36% of children and 62% of the adults tested (p less than 0.01). There was no relationship between ICA/ICSA and diabetes-associated HLA antigens, haptoglobin phenotype or beta cell function (fasting C-peptide and insulin response to 75 g oGTT). However, adults with circulating ICA were characterized by a significantly lower insulin response to glucose. Fifty two "risk" subjects characterized by IGT, diabetes associated HLA antigen(s), ICA or ICSA either alone or combined were studied again 26 months after mumps infection. No symptomatic diabetes appeared and IGT was diagnosed in one case only. ICA and ICSA persisted in more than 50% of subjects in whom ICA or ICSA were present 14 months after mumps infection. Since the used immunological techniques do not clearly distinguish organ-specific from non-organ-specific antibodies the results must be interpreted with caution. To summarize, the preliminary results do not support a close temporal relationship between mumps infection and the onset of IDDM. The pathogenetic role of mumps virus and ICA/ICSA and their possible relation to a slow progressive beta cell destruction has still to be determined.

Adult↗

Prevalence of islet cell antibodies (ICA) and islet cell surface antibodies (ICSA) in children and adolescents with antecedent mumps infection).

There is good evidence that viruses may play a role in some animal models of diabetes. Since mumps virus seems to be the most likely candidate, we studied the possible relationship of islet cell antibodies, islet cell surface antibodies and glucose tolerance in 86 children and adolescents in whom mumps infection had occurred 14 months previously. Impaired glucose tolerance was diagnosed in 3.5% (n = 3) but symptomatic diabetes did not appear. No relationship existed between complications of antecedent mumps infection (pancreatitis, orchitis, meningitis) and glucose tolerance. The prevalence of ICA and ICSA was 78% and 36%, respectively. The simultaneous prevalence of ICA and ICSA was 33%. The pathogenetic role of mumps infection and ICA/ ICSA and their possible relation to slow progressive beta cell destruction remains to be elucidated.

Adolescent↗

Antibody-dependent cell-mediated cytotoxicity of mononuclear cells against Langerhans islets of Wistar rats in normal man and in patients at diabetes risk.

Antibody-dependent cell-mediated cytotoxicity against pancreatic islets was investigated in 13 newly diagnosed insulin-dependent diabetics, in 38 patients at high risk for the disease and in 20 age-matched healthy controls. For this purpose 51Cr-labeled neonatal rat pancreatic islets incubated with the specific anti-rat islet cell antiserum 339 or with serum of the lymphocyte donors were used as targets. The antibody-mediated cytotoxic activity of mononuclear cells was evaluated from the specific chromium release after 6 h exposure of pretreated islets to the effector cells. The specific cytotoxic effect of mononuclear cells from healthy controls on pancreatic islets pretreated with serum is weak. ADCC mediated by the specific antirat islet cell antiserum is significantly increased in 54% of newly diagnosed diabetics as well as in 32% of patients at high risk for insulin-dependent diabetes mellitus. 46% of the newly diagnosed diabetics were also ADCC-positive when their own serum was used for the pretreatment of islets, regardless of whether they were islet cell antibody- or islet cell surface antibody positive or not. Subsets of mononuclear cells (non E-rosette-forming cells, high affinity E-rosette-forming cells, low affinity E-rosette-forming cells) were prepared and their cytotoxic potential was analysed in patients with positive ADCC test results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of clofibrate therapy on glucose tolerance, insulin secretion and serum lipids in subjects with hyperlipoproteinemia and impaired glucose tolerance. A follow-up study over a five-year period.

The long term effect of clofibrate treatment on the carbohydrate and lipid metabolisms and on insulin secretion was studied in subjects with primary hyperlipoproteinemia and impaired glucose tolerance. Treatment consisted of a diet and 2.0 g clofibrate per day. The body weight, triglyceride and cholesterol levels, glucose tolerance and insulin secretion of 14 patients were monitored for five years. During the first year of treatment the mean triglyceride and cholesterol levels decreased by 80% and 40% respectively. The cholesterol level became fully normal in the course of further treatment, but the triglyceride level did not. The mean reduction of body weight over the five-year period amounted to 5.0 kg. Improvement in glucose tolerance was shown by a significant increase in Conard's glucose assimilation coefficient. Glucose tolerance became completely normal in some cases. In one case diabetes mellitus became manifest. Improvement of the glucose tolerance was accompanied by reduction of glucose-stimulated insulin secretion by about 50% of the original value. The results permit the conclusion that the use of clofibrate for the long-term treatment of hyperlipoproteinemia is still justified. If hyperlipoproteinemia is accompanied by impaired glucose tolerance, clofibrate can also be regarded as having a certain antidiabetic effect during the normalisation of the "metabolic syndrome".

Adult↗

Insulin antibodies in juvenile diabetes mellitus. Correlations to diabetic stability, insulin requirement and duration of insulin treatment.

We investigated the plasma insulin binding patterns of 15 insulin-treated juvenile diabetics with a very low residual B-cell function. Determination of the insulin binding was performed after removal of therapeutic insulin. 125I-monoiodoinsulin was used and insulin binding was measured over a large range of insulin concentration. Insulin binding parameters were evaluated by Scatchard analysis of the binding data. Significantly elevated insulin binding was detected when the diabetic control was stable. These patients had a lower insulin requirement and low equilibrium dissociation constants of the high affinity antibodies. Furthermore, a strong negative correlation between the duration of insulin treatment and insulin binding could be demonstrated resulting from both decreasing antibody affinities and maximum binding capacities. We discuss the stabilizing effect of insulin antibodies on the metabolic character assuming that dissociating insulin-antibody complexes mimic a "basal insulin secretion" similar to pancreatic B-cells with residual functional capacity.

Adolescent↗

Regulation of pancreatic glucagon secretion during a continuous glucose infusion in early and overt diabetics.

The pancreatic glucagon (IRG) secretion pattern was studied during a 2 h glucose infusion test (12 mg/kg/min) in 21 controls as well as in 44 subjects showing different degrees of carbohydrate intolerance. The fasting IRG levels increased significantly from controls (98 +/- 7.6 pg/ml) to chemical (144 +/- 9 pg/ml) and mild maturity-onset-type diabetics (166 +/- 12.2 pg/ml). During artificial hyperglycaemia the glucagon concentrations decreased slightly in all groups, but they remained at a higher level in early and overt diabetics). The molar IRI-IRG ratios have been found to be diminished in patients displaying a disturbed carbohydrate tolerance. There was not any correlation between insulin and glucagon concentrations in the blood. The findings suggest that abnormalities of alpha cell function may be present in early and overt diabetes independent of beta cell responsiveness. The causal relationship of A and B cell function in glucose intolerant subjects has to be cleared in follow-up studies.

Adult↗

[Necrobiosis lipoidica diabetricorum and serum lipids].

Necrobiosis lipoidica diabeticorum is briefly described. Its high coincidence with hyperlipoproteinaemia in casuistic reports from the literature as well as in about half of the 22 cases observed in our clinic can be taken in favour of possible relations between these conditions. Disturbances of fat metabolism may even be considered important for pathogenesis of necrobiosis in general, the more as at least no optimally regulated fat and carbohydrate metabolism can be achieved by best therapeutic control of carbohydrate parameters in juvenile diabetics. Microangiopathia diabetica seems to exist from the very beginning of diabetes mellitus and may ne a basic etiologic prerequisite for the development of necrobiosis. Topical conditions of certain body regions are said to take part in final precipitation of necrobiotic spots.

Adult↗

[Hyperlipoproteinemia -- cause or sequelae of maturity-onset diabetes].

With the help of data from literature and own long-term observations the importance of the hyperlipoproteinaemias (HLP type IIb-V) as precursors of the maturity-onset-diabetes is discussed. The assumption of transitions of the hyperlipoproteinaemias with insignificant disturbances of the carbohydrate tolerance and hyperinsulinism into a condition with manifest diabetes mellitus and relative lack of insulin appears justified. Differential diagnostics (e.g. by determination of the insulin response after glucose tolerance) and adequate differential therapy of the symptom complex belonging to the metabolic syndrome are demanded.

Adult↗