The in vivo visualization of insulitis. A new marker of prediabetes.
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Animals↗
Biomedical subjects
D Andreani
Publications and source records attributed to D Andreani.
Quantitative immunological differences between newly diagnosed Graves' disease patients and relapsed patients.
Class 2-positive T cells, T-cell and mononuclear cell subsets, thyrotropin receptor antibodies (TRAb) and immune complexes were evaluated in 34 newly diagnosed Graves' patients and in 13 relapsed patients before a cycle of specific medical treatment. Class II-positive T lymphocytes were detected by monoclonal antibodies against different epitopes of class II antigens, whereas 4F2-positive cells were detected by 4F2 monoclonal antibody. 4F2-positive cells were statistically increased in newly diagnosed Graves' patients compared to relapsed patients (p less than 0.05). An increased percentage of class II activated T cells, detected by monoclonal antibodies L243, was found in newly diagnosed patients in comparison with relapsed subjects (p less than 0.025). Newly diagnosed Graves' patients showed a significant decrease in the ratio suppressor/cytotoxic T cells in comparison with normal control subjects but not with relapsed patients. Ninety-one % of newly diagnosed Graves' patients showed a high TRAb value, whereas only 69% of relapsed patients showed increased values (p less than 0.025). No difference was observed in the immune complex positivity between newly diagnosed Graves' patients and relapsed subjects. In conclusion, both humoral and cellular immune differences were found in relapsed patients vs newly diagnosed Graves' patients. The immunological abnormalities are quantitatively more pronounced in the latter group.
Adolescent↗
Statement on post-prandial or reactive hypoglycaemia.
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Blood Glucose↗
Synthesis and release of insulinlike growth factor I by mesangial cells in culture.
Mesangial cell proliferation is a common hallmark of many glomerular diseases. The exact mechanisms inducing cell proliferation in glomerulosclerosis are not completely understood, and it remains to be determined whether growth factors play a role in this process. Insulinlike growth factor I (IGF I) has been shown to be synthesized in the kidney, and glomerular mesangial cells have receptors for and exhibit mitogenic response to IGF I. We found that mouse glomerular mesangial cells in culture synthesized and released into the culture medium a molecule with immunological and biological features of IGF I. This molecule specifically bound to mesangial cell IGF I receptors; high-pressure liquid chromatographic analysis provided further evidence of its similarity to human recombinant IGF I. Mesangial cells released into the culture medium 6 ng/10(6) cells of IGF I-like material per 24 h in a time-dependent and actinomycin-D inhibitable fashion. These data suggest that IGF I might be locally released by mesangial cells in the glomerulus and act in an autocrine and paracrine fashion.
Animals↗
Circulating anti-immunoglobulin antibodies in recent-onset type I diabetic patients.
Human sera from 51 recent-onset insulin-dependent (type I) diabetic patients and 47 unrelated control subjects were screened for the possible presence of circulating factors reacting with several anti-pancreatic islet monoclonal antibodies (MoAb.ISL) in solid-phase radioimmunoassay methods (the original goal being the detection of anti-idiotypic islet cell antibodies and/or specific islet cell antigen-bearing immune complexes). MoAbs from the parental myeloma cell line and purified immunoglobulins (Igs) from different animal species were controls. Type I diabetic sera showed significantly increased binding to MoAb.ISL-coated wells compared with normal subjects (P less than .001). However, the same sera also tended to show a higher binding to the control (non-islet-related) MoAb. Sera from type I diabetic patients also reacted with horse, bovine, pig, rabbit, and goat IgG. Displacement of the binding has been obtained by F(ab')2 and/or Fc fragments of IgG. Evidence has been obtained regarding a similar reaction with human IgM. All the sera were negative when tested for rheumatoid factor by nephelometry. The circulating antibodies described have been proven to be different from islet cell autoantibodies. An anti-Ig antibody is thus present in the sera of recent-onset diabetic patients and represents an additional immunological phenomenon with possible physiopathological and clinical significance.
Adult↗
Renal hemodynamics and urinary excretion of 6-keto-prostaglandin F1 alpha and thromboxane B2 in newly diagnosed type I diabetic patients.
We have studied the functional importance of renal eicosanoids in renal hemodynamics of seven newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients by treatment with two structurally unrelated inhibitors of cyclooxygenase (i.e., piroxicam and sulindac). Glomerular filtration rate (GFR), renal plasma flow (RPF), daily urinary excretion of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha, the stable hydrolysis product of prostacyclin), and thromboxane B2 (TXB2, the stable hydrolysis product of thromboxane A2) were measured before, during, and after piroxicam (all patients) or sulindac (3 patients) treatment. Urinary excretion of 6-keto-PGF1 alpha was significantly increased (P less than .01) in diabetic patients compared with seven healthy subjects, whereas urinary excretion of TXB2 was unchanged. The baseline value of GFR was significantly (P less than .01) higher in diabetic compared with normal volunteers, whereas baseline RPF was comparable in both groups. Piroxicam (20 mg/day) reduced urinary excretion of 6-keto-PGF1 alpha and TXB2 by 65.7 +/- 26 and 64.6 +/- 33%, respectively. These biochemical changes were temporally associated with the approximately 19% decrease in GFR (P less than .01). A week after discontinuation of the drug, GFR and urinary excretion of 6-keto-PGF1 alpha were still significantly (P less than .05) reduced, whereas urinary excretion of TXB2 returned to control values. In contrast, urinary excretion of eicosanoids and renal function were not affected by sulindac (0.4 g/day) treatment. No functional changes were detected in healthy subjects despite a similar suppression of renal cyclooxygenase activity when they were treated with piroxicam.(ABSTRACT TRUNCATED AT 250 WORDS)
6-Ketoprostaglandin F1 alpha↗
Statement on postprandial hypoglycemia.
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Blood Glucose↗
Early detection of neurological involvement in IDDM and NIDDM. Multimodal evoked potentials versus metabolic control.
Clarification of the extent and mechanisms of damage to the central nervous system in diabetes is a frontier of current neurological research. Our aim was to obtain ample electrophysiological documentation of possible neurological abnormalities in both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients with a short duration of disease and without overt complications, taking into account metabolic control. Group 1 comprised 11 IDDM patients, and group 2 included 14 NIDDM patients treated with diet alone; the duration of disease was less than 4 yr, and no concomitant clinical complications were present. Age- and sex-matched normal subjects formed groups 3 and 4. Pattern visual evoked potentials (VEP), brain stem auditory evoked potentials (BAEP), and somatosensory evoked potentials (SEP; after the stimulation of both median and tibial nerves) were recorded in all subjects, and metabolic control was evaluated in terms of glycemia and glycosylated hemoglobin. In group 1, significant abnormalities were found in the latency values of VEP, median SEP, and tibial SEP compared with control subjects. Similar latency abnormalities were shown in group 2 for VEP, median SEP, and tibial SEP values and for wave I latency of BAEP. Glycosylated hemoglobin values were correlated with BAEP and SEP abnormalities in many patients in both groups. Furthermore, in group 2, glycemic values correlated with SEP abnormalities. We therefore conclude that neurophysiological abnormalities are present at different levels in IDDM and NIDDM patients only a few years after clinical diagnosis and before the appearance of overt complications, and these abnormalities seem to be correlated with metabolic control status.
Adult↗
Detection of activated lymphocytes in endocrine pancreas of BB/W rats by injection of 123I-interleukin-2: an early sign of type 1 diabetes.
Recombinant interleukin-2 (IL2) was labelled with iodine-123 by a modified chloramine T method. The labelled IL2, which had a high specific activity (100-150 microCi/microgram) and retained its capacity for binding to the IL2 receptor on activated lymphocytes in vitro, was injected intravenously into BB/W diabetes-prone and normal rats. Combined immunoperoxidase staining and autoradiography of organ sections revealed that labelled IL2 bound specifically in vivo to IL2-receptor-positive cells in the spleen of both normal and BB/W rats and to activated lymphocytes infiltrating the pancreas of BB/W rats. The severity of lymphocytic infiltration correlated with the degree of radioactivity in the pancreas of BB/W rats. Time-activity curves, generated over organs of injected rats after gamma camera imaging, confirmed that radioactivity was greater in the pancreas of diabetes-prone than in normal rats. 123I is a suitable isotope for gamma camera imaging, so the intravenous injection of IL2 labelled with iodine-123 may be valuable for the in-vivo visualisation of activated lymphocytes in tissues infiltrated by lymphocytes.
Animals↗
Immunology in diabetic pregnancy: activated T cells in diabetic mothers and neonates.
Lymphocytes bearing surface antigens indicating early and full activation have been evaluated, in addition to T cell subsets, in blood samples from diabetic pregnant patients, neonates from diabetic mothers and control groups. The type of diabetes and the trimester of pregnancy were taken into account. Monoclonal antibodies were used to enumerate total T cells, helper/inducer, cytotoxic/suppressor Tlymphocytes and activated mononuclear cells using antibodies binding lymphocyte surface antigens as markers of early lymphocyte activation, and MHC Class II surface antigens as markers of late activation. A decrease in T-helper cells during the third trimester of pregnancy in Type 1 (insulin-dependent) and gestational diabetic patients (p less than 0.02) and a decrease in T-suppressor cells in Type 2 (non-insulin-dependent) diabetic pregnant patients during the third trimester (p less than 0.01) were observed in relation to normal values. As in normal pregnancy, 4F2-positive cells were increased in 48% of diabetic pregnant patients during the second and third trimesters of gestation. Class II-positive cells were increased in almost 60% of Type 1 and gestational diabetic patients during the last trimester of pregnancy in comparison with normal pregnant women and control subjects. A decrease in T-helper cells (p less than 0.02) and a clear increase in 4F2-positive cells (p less than 0.001) and Class II-positive lymphocytes (p less than 0.005) were observed in the infants of diabetic mothers in comparison with control subjects. The maternal cellular immune system, actively altered in pregnancy, is fully activated in a number of Type 1 and gestational diabetic pregnant patients. Activated lymphocytes are even found in the neonates of diabetic mothers, but these do not trigger the events leading to the onset of diabetes in the short term.
Adult↗
Reduced protection against hepatitis B virus following vaccination in patients with type 1 (insulin-dependent) diabetes.
Twenty patients with well controlled Type 1 (insulin-dependent) diabetes of at least 10 years duration and 47 control subjects were vaccinated against the hepatitis B virus using the Hevac B vaccine. The vaccine was administered into the deltoid region on three occasions at intervals of 1 month. Thereafter a fourth dose was given to subjects still negative for antibody to hepatitis B surface antigen (HbsAb). The median rise of HbsAb titres was 230 mIU/ml in normal subjects and 50 mIU/ml in diabetic patients (p less than 0.001). Eight patients (40%) failed to reach HbsAb titres above 30 mIU/ml, the level considered to give optimal protection against the infection, whereas only one normal control subject failed to reach this level. Five patients (25%) showed no response despite a fourth dose of the vaccine. There was an increased frequency of HLA-DR7 in low responders and a decreased (less than 1.5) helper/suppressor lymphocyte ratio. Diabetic patients are thus less likely to mount a protective antibody response following vaccination against hepatitis. Since hepatitis B surface antigen is reported to be considerably more common in diabetic patients than control subjects, infection with hepatitis B virus may have a greater risk of chronicity in diabetes.
Adult↗
Humoral and cellular immune abnormalities in neonates of diabetic mothers: any pathological role?
Insulin antibodies, insulin complexes, T-cell subsets and T-cells bearing surface antigens indicating early activation were studied in 35 and 24 infants of diabetic and of normal mothers respectively, which were compared with normal adult control subjects. Anti-insulin antibodies were evaluated using a modified version of Andersen's method, insulin complexes were assessed by a method developed by us; total T cells, helper/inducer and cytotoxic/suppressor T lymphocytes, and early activated T lymphocytes were determined using the monoclonal antibodies OKT3, OKT4, OKT8 and 4F2 respectively. The presence of insulin antibodies was correlated to macrosomia, hypoglycaemia and respiratory distress syndrome. Insulin-anti-insulin complexes were found in some of the neonates and were likely to have been formed by maternal antibodies and insulin from the neonate. Modifications of T-cell subsets were found in the neonates both of diabetic and of normal mothers. --Despite the presence of these immune abnormalities in some infants of diabetic mothers, the clinical onset of diabetes was not diagnosed in any of the cases studied. Nevertheless, the immunological abnormalities in neonates of diabetic mothers have short-term pathogenetic effects which raises the question of their possible long-term effect.
Adult↗
Normalization of the CD4/CD8 lymphocyte ratio and increased B lymphocytes in long standing diabetic patients following therapy with thymopentin.
A double blind study with thymopentin (TP5) and placebo was performed in 49 patients affected by Type 1 and Type 2 diabetes of long duration characterized by a reduction of the CD4/CD8 (helper/suppressor) lymphocyte ratio. TP5 (50 mg) was administered subcutaneously 3 times weekly for 1 month. Total peripheral lymphocytes and functionally different cell subsets were measured throughout the course of the study. Data showed a statistically significant increase of the CD4/CD8 lymphocyte ratio (p less than 0.02) and of the percentage of B lymphocytes (p less than 0.001) only in the TP5 receiving group. No side effects were observed during the study and patients remained well controlled. These results suggests that TP5 may be administered safely to diabetic patients and by improving impaired cell mediated immune parameters TP5 may contribute to prevent the development of infections in these patients.
Adult↗
In vivo determination of cell mediated immune response in diabetic patients using a multiple intradermal antigen dispenser.
The in vivo cell mediated immune response using a multiple intradermal antigen dispenser (Multitest) was evaluated in 99 diabetic patients (24 Type I and 75 Type II) and in 50 age matched normal subjects. Seven different antigens (tetanus, diphteria, streptococcus, tubercoline, candida, trichophyton, proteus and a glycerine control) were applied in the forearm and the induration for the antigens tested was measured 48 hours later. A score was calculated adding the arithmetic means obtained with each single antigen. Overall we did not find major differences between diabetic patients and controls except Type I patients of shorter duration (less than 5 years) having a reduced response (p less than 0.05) and both Type I and Type II patients showing an elevated response to candida antigen (p less than 0.001). No correlation was found between the intradermal response and metabolic control. As the intradermal test is a model for delayed type of hypersensitivity, these data suggest that the in vivo lymphocyte to lymphocyte cooperation in patients with long standing diabetes is not impaired.
Adult↗
The immune response to influenza vaccination in diabetic patients.
The immune response of diabetic patients to influenza vaccination was examined in 31 patients, 10 with Type 1 (insulin-dependent) diabetes and 21 with Type 2 (non-insulin-dependent diabetes), and in 19 normal subjects. Each received a single intramuscular injection of the 3 virus strains (A/Chile,A/Philippines,B/USSR) anti-influenza vaccine recommended by WHO. The antibody titre and the cell-mediated immune response to the 3 virus strains, as evaluated by the generation of activated lymphocytes and enumeration of B lymphocytes, were studied before and 18 h, 72 h and 1, 2, 3 and 6 weeks after vaccination. Overall, the humoral and cell-mediated immune responses were normal in both groups of patients. However, patients with Type 1 diabetes showed a statistically significant increase (p less than 0.01) of antibody titre of the A/Chile and an increased percentage of B lymphocytes one week after vaccination compared to age-matched control subjects. Four out of 21 patients with Type 2 diabetes had no antibody response to all 3 virus strains. A significant reduction (p less than 0.01) of the percentage of activated cells possessing receptors for interleukin-2 was observed 72 h after vaccination in patients with Type 2 diabetes compared to age-matched control subjects. None of the patients who received the vaccine developed influenza in the course of the following year. These results suggest that valid protection against the influenza virus can be obtained in patients with Type 1 and Type 2 diabetes.
Adult↗
A sensitive routine assay for urinary albumin based on the competitive binding to anti-albumin antibodies in solid phase.
The detection of microalbuminuria has a high prognostic value in diabetic patients with no symptoms of clinical nephropathy. Attention has been focused on the development of a simple, reproducible, specific, and, above all, sensitive method to detect albuminuria in the urine. The method is based on the competitive binding between albumin in the urine to be tested and a fixed amount of radiolabelled albumin to anti-albumin immunoglobulins in solid phase. The immunoglobulin C fraction of a rabbit anti-human albumin antiserum was left to coat highly adsorbent polystyrene microtitre tubes. While the aspecific tube binding was overcome by saturation with a solution of gelatine, increasing dilutions of standard albumin or the diluted urine samples to be tested were left to incubate with an equal volume of radiolabelled albumin at room temperature for 1 hour. The cold/hot albumin mixture was added to anti-albumin immunoglobulin-coated tubes, which had been repeatedly washed, and left to incubate. After washing, radioactivity was assessed. This assay has proved to be fast, simple and highly sensitive since it detects up to 25 ng of albumin per ml and is of value in large-scale screening for microalbuminuria in diabetic patients.
Albumins↗
Immunity in Graves' disease at diagnosis: correlation between activated T cells and humoral immune factors.
Activated T cells, T-cell subsets, thyrotropin receptor antibodies and immune complexes were evaluated in 31 patients with newly diagnosed Graves' disease. Activated T cells were assayed by monoclonal antibodies against early (4F2) and late activation surface lymphocyte antigens (different epitopes of class II antigens). In comparison with the normal population, Graves' patients showed a significant decrease in the suppressor cytotoxic T-cell subset. Significant increases of 4F2-positive cells (70% of patients studied), class II antigen-positive cells (65%), thyrotropin receptor antibodies (93%), Clq-immune complexeses (44%) and conglutinin-immune complexes (37%) were observed. A significant inverse correlation between the increase in 4F2-positive cells and thyrotropin receptor antibody values was also observed. Lymphocytes from Graves' patients were cultured in the presence of thyrotropin receptor antibody-positive or -negative sera, with or without mitogen stimulation. Thyrotropin receptor antibodies were shown not to interfere with the expression of activation antigens in cultured cells. The different patterns of humoral and cellular immune phenomena may indicate the existence of either different stages of Graves' disease or a heterogeneity of the immunopathogenesis in different patients.
Adolescent↗
White cells transfusion in recent onset type 1 diabetes.
Two HLA-identical brothers developed Type 1 diabetes simultaneously. In the light of present knowledge of the pathogenesis of Type 1 diabetes, immunosuppression was adopted in one brother by means of white cell transfusion from the father. The other brother acted as a control. This immunosuppressive approach has been shown to be effective in kidney transplantation and, as far as Type 1 diabetes is concerned, in the BB Wistar rat. An immunological and metabolic follow-up study of 1 yr only revealed slight differences between the 2 brothers (who are both on insulin) but the pattern of lymphocyte activation appeared to become normalized earlier in the transfused brother.
Adolescent↗