[C-peptide levels in secondary sulfonylurea resistant diabetics]. / Késöi sulfonylurea resistens cukorbetegek serum C-peptid szintjének vizsgálata.

In the presence of clinical features of secondary drug failure--even after reeducation on diet and intensive control of patients--is difficult to make a decision to switch on insulin. Therefore the serum C-peptide concentrations were assessed in order to get supporting data. From 35 patients with suspected secondary drug failure the therapy of 11 patients was continued with insulin, 24 patients remained on glibenclamide therapy. The decision based on clinical criteria. All of the patients were studied in i.v. glucagon test and with a test meal to evaluate their basal and stimulated serum C-peptide concentrations. There were only three patients with subnormal basal C-peptide (< or = 0.30 nmol/l), on the other hand nine patients had lower post-glucagon serum C-peptide level than 0.60 nmol/l. The basal and stimulated C-peptide concentrations from i.v. glucagon test and test-meal indicated the need of insulin therapy with a sensitivity of 81.8 percent and with specificity of 70.8 percent. The further glibenclamide treatment on the basis of C-peptide concentrations in 89.5 percent of cases could be accurately established. The statistical analysis showed that the glucagon-stimulated C-peptide concentration was the most characteristic feature to discriminate the patients in order to make a decision on the further diabetes therapy.

The effect of azathioprine, cyclosporine A and insulin on the in vitro lymphocyte-mediated cytotoxicity in type I diabetic patients.

Previously both specific and nonspecific immune reactions have been reported in patients with type I diabetes mellitus. In this study the effect of various immunosuppressive drugs and insulin was studied on in vitro lymphocyte-mediated cytotoxicity in 20 type I diabetic patients. Twenty sex- and age-matched healthy subjects served as controls. Human pancreas-extract (300 micrograms/ml protein)-coated, 51-Chromium labeled chicken erythrocytes were used as target cells and separated T-lymphocytes as effector cells with and without azathioprine 50 micrograms/50 microliters (Wellcome), Cyclosporine A 5 ng/50 microliters (Sandoz) and MC Actrapid insulin 0.1 IU/50 microliters (Novo). The degree of cytotoxicity was expressed with cytotoxic capacity: the number of maximal killed target cells. Simultaneously islet cell antibodies (ICA) in sera and the number of activated T-lymphocytes were assessed. Significant lymphocyte-mediated cytotoxicity was observed in the majority of type I diabetic patients (18/20), while no cytotoxicity was found in the control cases. The cytotoxicity decreased in all 16 patients using azathioprine or insulin, independently of ICA and HLA-DR positivity. The number of killed target cells was lowered considerably by Cyclosporine A in all 18 patients having cytotoxicity against pancreas-extract. Our observations reveal that Cyclosporine A proved to be the most effective immunosuppressive agent in vitro. It decreases not only the leucocyte migration inhibition as previously observed, but also the lymphocyte-mediated cytotoxicity, which represents the late stage of cellular immune reactions against pancreatic tissue.

Human pancreatic extract and rat pancreatic islet homogenate-coated chicken erythrocytes as targets of lymphocyte-mediated cytotoxicity in type I diabetic patients.

In this study 51Cr-labeled chicken erythrocytes coated with human pancreatic extract or rat pancreatic islet homogenate served as target cells for the detection of lymphocyte-mediated cytotoxicity in type I-diabetics. T-lymphocytes from type I-diabetic patients showed a significant cytotoxic capacity against target cells coated with human antigens as well as rat pancreatic islet homogenate. The frequency and intensity of cytotoxicity proved to be similar against the two types of targets. Since rat pancreatic islets are easily available and contain more characteristic beta-cell antigens than human pancreas extract, the homogenate of rat islets of Langerhans is more suitable than human pancreatic extract for studying the lymphocyte-mediated cytotoxicity in type I-diabetic patients.

Immune reactions in patients with type I and with type II diabetes mellitus.

Since several data refer to the role of immune processes in the pathogenesis of diabetes mellitus, this study was performed to compare aspecific and specific immune reactions in type I- and in type II diabetic patients over a six month period. The percentage and the absolute number of SRBC-rosette forming active E(A), of theophylline-resistant E(Thr) and of ORCB-rosette forming T(M)-cell subsets proved to be elevated in newly diagnosed type I but reduced in type II diabetic patients. Also an elevated percentage of HLA-DR positive, activated T cells was found in the majority of recent-onset type I diabetics. In the presence of human pancreas extract, a significant inhibition of leucocyte migration, a pronounced and specific cytotoxic capacity of all lymphocyte subsets (especially of the T(G)-cells), and elevated antibody titers (passive haemagglutination, indirect immunofluorescence) were observed in almost all type I diabetics, but only in a few cases of type II patients. After six months, the frequency both of the aspecific and of the specific immune parameters was decreased in type I diabetics, but no changes were observed in the type II diabetics with a previously positive test. The latter patients required insulin therapy at the time of the second investigation. The leucocyte migration inhibition test and the lymphocyte-mediated cytotoxicity are suitable for studying in-vitro-sensitization against pancreatic tissue and they might predict later insulin-dependency in type II diabetic patients.

T-lymphocyte subsets and their cytotoxic capacity in patients with type I and type II diabetes mellitus.

Distribution and cytotoxic function of lymphocyte subpopulations were studied in 20 patients with type I, in 20 patients with type II diabetes mellitus and in 40 control subjects. The percentage, the absolute number of (EA), (E Thr), (TM) subsets and the rate of (E Thr) (E Ths) and (TM/) (TG) cells were found to be higher in type I and lower in type II diabetic patients than in controls. This opposite tendency in the distribution of T-lymphocyte subsets may be related to the duration of diabetes. Simultaneously a significant cytotoxic capacity of U, null, T, (TG)-lymphocytes was observed against human pancreas extract-coated targets in almost all 18 out of 20 of type I, but only in a few cases (5 out of 20) of type II diabetic patients. These five patients needed insulin therapy six months later. The T and (TG)-lymphocytes had the largest killer activity in both diabetic groups. Lymphocyte-mediated cytotoxicity seems to be a specific method which is suitable for the study of in vitro sensitization against pancreas tissue, and it might predict insulin dependency in type II diabetic patients.

Serum lipids during starvation in obesity.

The HDL-cholesterol level was found to decrease during the first week of therapeutic starvation in hyperlipoproteinaemic (hypertriglyceridaemic), diabetic (non-insulin dependent) patients. The possible causes of the finding are discussed, and the view is expressed that the fall in HDL given no cause for discontinuing the caloric restriction or starvation as the therapeutic measures in obesity.

Alterations of the basal serum insulin and blood glucose in brain-injured patients.

Serial fasting blood glucose and basal serum insulin were measured in brain-injured patients. The endocrine changes were compared with the level of consciousness. Evaluating the serial examinations of 92 brain-injured and 31 control patients we came to the following conclusions. There is a quantitative correlation between the alterations in the level of consciousness and the fasting blood-glucose and serum-insulin levels in brain-injured patients. Deep coma is connected with a high blood-sugar level, clear consciousness with a normal glucose level. The insulin level is, however, decreased in the comatose state and normal in the state of clear consciousness. According to the alterations in blood-glucose and insulin levels, brain-injured patients can be divided into four groups. The alterations in the insulin level cannot give a proper explanation of the blood-sugar changes. Some changes in the levels of both blood glucose and serum insulin may have prognostic significance. According to our results it can be supposed that certain cerebral structures take part in the regulation of the basal insulin secretion.

Basal and insulin-stimulated glucose metabolism of isolated human fat cells.

Glucose-U-14C-activity added to the incubation medium of isolated human fat cells was studied for its conversion to CO2 and its incorporation into fat cell triglyceride. In view of the wide scatter of the figures found under basal conditions as well as in the presence of 100 muU/ml of insulin, the correlations of fat cell glucose metabolism to ponderal index, total body fat mass weight, mean fat cell diameter, fat cell TG-content and age were analysed. The activity of glucose metabolism in obese individuals was found to be inversely related to the degree of obesity under basal conditions as well as under the effect of insulin. According to partial regression analysis, of all these parameters it was the ponderal index which showed the most significant inverse correlation to the activity of fat cell glucose metabolism. No appreciable relationship was found between the production of CO2 from glucose and age. Incorporation of 14C-activity into fat cell triglyceride showed a slight age-related increase under basal conditions as well as on insulin stimulation. It is concluded that at the cellular level it is the triglyceride saturation of fat cells which constitutes the endogenous regulatory factor responsible for the impaired biological action exerted by insulin on the enlarged fat cells in obesity.

Carbohydrate metabolism in various types of hyperlipoproteinaemia.

Insulin secretion has been studied after an oral glucose load in 81 patients with primary hyperlipoproteinaemia and 15 control sugjects. Glucose tolerance was reduced mainly in Type IV, and to a lesser extent in Type IIB hyperlipoproteinaemia. Insulin secretory response to glucose was reduced in Type V and heterogeneous in Type IV hyperlipoproteinaemia. No correlation was found between the triglyceride level and the rate of insulin secretion.