Biomedical subjects
Publications and source records attributed to G d'Annunzio.
Explore the source record for details and available documents.
In type 1 diabetes mellitus (T1DM), cytokines can be directly cytotoxic to beta-cells, and/or play an indirect role influencing some cells of the immune system. Since several factors could impair cytokine serum levels, the purpose of our study was to longitudinally evaluate intracellular cytokines, in T1DM patients, and in subject at risk, by flow cytometry analysis. At T1DM onset we observed significantly lower percentage of peripheral CD4 + and CD8 + cells producing IFN-gamma in patients compared to controls and subjects at risk. The 15-month follow-up patients showed significantly lower percentage of CD4 + and CD8 + cells producing IFN-gamma compared to the other groups. At 8-year follow-up no significant differences were observed among the groups in the percentage of cells producing cytokines. We could have considered "exhausted cells" or these T cell subsets may be migrated from peripheral blood to pancreas. On the other hand, our results are in agreement with those reported in literature: in animal model the absence of IFN-gamma production makes beta-cells highly susceptible to viral infection and subsequent attack by natural killer cells, which lead to hyperglycaemia and diabetes mellitus.
In the context of the EU funded Telematic Management of Insulin-Dependent Diabetes Mellitus (T-IDDM) project, we have designed, developed and evaluated a telemedicine system for insulin dependent diabetic patients management. The system relies on the integration of two modules, a Patient Unit (PU) and a Medical Unit (MU), able to communicate over the Internet and the Public Switched Telephone Network. Using the PU, patients are allowed to automatically download their monitoring data from the blood glucose monitoring device, and to send them to the hospital data-base; moreover, they are supported in their every day self monitoring activity. The MU provides physicians with a set of tools for data visualization, data analysis and decision support, and allows them to send messages and/or therapeutic advice to the patients. The T-IDDM service has been evaluated through the application of a formal methodology, and has been used by European patients and physicians for about 18 months. The results obtained during the project demonstration, even if obtained on a pilot study of 12 subjects, show the feasibility of the T-IDDM telemedicine service, and seem to substantiate the hypothesis that the use of the system could present an advantage in the management of insulin dependent diabetic patients, by improving communications and, potentially, clinical outcomes.
The purpose of this study was to evaluate, through a meta-analysis study, whether the use of computer-based systems reported in the literature improves the metabolic control of diabetic patients. On the retrieved papers, a set of meta-analysis studies were performed: first the difference of HbA1c between cases and controls at follow-up was evaluated (sign test); then the difference between cases and controls in the total variation of HbA1c from the beginning to the end of the trial was considered (method of effect sizes). The latter methodology was reapplied also on three more homogeneous article subgroups. The sign test was performed on 16 papers: in two of them, the HbA1c level was higher in the intervention group than in the control group at follow-up: it is unlikely that this is a random occurrence (p < 0.01). The method of effect sizes was first applied to 13 papers, as in the others some needed data were missing: the results obtained showed a statistically significant amelioration of metabolic control in the intervention group in comparison to the control group (p < 0.01). A progressive reinforcement of this outcome was obtained on the trial subgroups. Our study supports the hypothesis that the use of computer-based systems can be an effective means of improving metabolic control. The differential benefit obtained in the amelioration of HbA1c does not justify, by itself, the applicability of such systems into clinical practice; additional investigations should be carried out to evaluate the enhancement of other clinical and organizational indicators.
OBJECTIVE: The aim of our study was to determine whether children with incidental hyperglycemia are at an increased risk of developing type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 748 subjects, 1-18 years of age (9.04 +/- 3.62, mean +/- SD), without family history of type 1 diabetes, without obesity, and not receiving drugs were studied and found to have incidental elevated glycemia defined as fasting plasma glucose >5.6 mmol/l confirmed on two occasions. Subjects were tested for immunological, metabolic, and immunogenetic markers. RESULTS: Islet cell antibodies >5 Juvenile Diabetes Foundation units were found in 10% of subjects, elevated insulin autoantibody levels in 4.6%, GAD antibody in 4.9%, and anti-tyrosine phosphatase-like protein autoantibodies in 3.9%. First-phase insulin response (FPIR) was <1st centile in 25.6% of subjects. The HLA-DR3/DR3 and HLA-DR4/other alleles were more frequent in hyperglycemic children than in normal control subjects (P = 0.012 and P = 0.005, respectively), and the HLA-DR other/other allele was less frequent than in normal control subjects (P = 0.000027). After a median follow-up of 42 months (range 1 month to 7 years), 16 (2.1%) subjects (11 males and 5 females), 4.1-13.9 years of age, became insulin dependent. All had one or more islet autoantibodies, and the majority had impaired insulin response and genetic susceptibility to type 1 diabetes. Diabetes symptoms were recorded in 11 patients and ketonuria only in 4 patients. The cumulative risk of type 1 diabetes was similar in males and females, and it was also similar in subjects under or over 10 years, whereas the cumulative risk of type 1 diabetes was increased in subjects with one or more autoantibodies and in those with FPIR <1st centile. CONCLUSIONS: Children with incidental hyperglycemia have a higher-than-normal frequency of immunological, metabolic, or genetic markers for type 1 diabetes and have an increased risk of developing type 1 diabetes.
The aim of the present study was to evaluate the persistence of anti-hepatitis B protective levels in young patients with type 1 diabetes, successfully immunised with a recombinant hepatitis B vaccine. We re-evaluated, after a 4 year follow-up, 54 patients and 70 age and sex-matched healthy subjects. Protective antibodies levels were found in 50/54 (92%) patients and in 67/70 (96%) controls. Moreover, anti-HBs levels were similar in diabetic patients and controls (means of log-titre and (sd); 1.95 (0.88) and 2.18 (0.64) patients and controls, respectively; P=0.11). No cases of clinical hepatitis were reported and all patients and controls remained HBc negative. These data demonstrate the persistence of anti-HBs levels in children, adolescents and young patients with type 1 diabetes after recombinant hepatitis B vaccine showing evidence of longterm immunogenity and protective effect.
Explore the source record for details and available documents.
In this paper we propose a case-based decision support tool, designed to help physicians in 1st type diabetes therapy revision through the intelligent retrieval of data related to past situations (or 'cases') similar to the current one. A case is defined as a set of variable values (or features) collected during a visit. We defined taxonomy of prototypical patients' conditions, or classes, to which each case should belong. For each input case, the system allows the physician to find similar past cases, both from the same patient and from different ones. We have implemented a two-steps procedure; (1) it finds the classes to which the input case could belong; (2) it lists the most similar cases from these classes, through a nearest neighbor technique, and provides some statistics useful for decision taking. The performance of the system has been tested on a data-base of 147 real cases, collected at the Policlinico S. Matteo Hospital of Pavia. The tool is fully integrated in the web-based architecture of the EU funded Telematic management of Insulin Dependent Diabetes Mellitus (T-IDDM) project.
OBJECTIVE: The aim of our study was to determine whether serum TNF-alpha levels in individuals at risk of developing type 1 diabetes, such as first-degree relatives of diabetic patients and children with incidental hyperglycemia, underwent alterations, and also to establish whether these levels might be used to identify individuals prior to insulin dependence. RESEARCH DESIGN AND METHOD: We studied 71 healthy first-degree relatives (FDR) of type 1 diabetic patients and 11 children with incidental hyperglycemia. We looked for immunogenetic (HLA class II serologic alleles and HLA-DQ alpha/beta genomic polymorphisms), immunologic (islet-cell and insulin autoantibodies) and metabolic (FPIR to IVGTT) markers of type 1 diabetic risk. Serum concentrations of TNF-alpha were quantified using IRMA. RESULTS: We found significantly lower serum TNF-alpha levels in FDR of type 1 diabetic patients (median: 54.3 pg/ml) (p=0.01) and in children with incidental hyperglycemia (median: 10.83 pg/ml) (p<0.0001) compared to controls (median: 76.56 pg/ml). No significant difference was observed between subjects with or without immunogenetic, immunologic and metabolic markers of type 1 diabetic risk. A negative correlation was found between serum TNF-alpha and HbA1c levels (r=-0.27, p=0.023). Two children with incidental hyperglycemia, whose TNF-alpha levels were very low, developed type 1 diabetes 6 and 8 months after this study. CONCLUSION: Our results are compatible with an impaired immune system in the prediabetic period and suggest that serum TNF-alpha concentrations may be considered as an immunological marker useful to identify subjects at risk of developing type 1 diabetes.
We propose a system for teleconsultation in Insulin Dependent Diabetes Mellitus (IDDM) management, accessible through the use of the net. The system is able to collect monitoring data, to analyze them through a set of tools, and to suggest a therapy adjustment in order to tackle the identified metabolic problems and to fit the patient's needs. The therapy revision has been implemented through the Episodic Skeletal Planning Methodi, it generates an advice and employs it to modify the current therapeutic protocol, presenting to the physician a set of feasible solutions, among which she can choose the new one.
Explore the source record for details and available documents.
In this paper we present a tool for the intelligent retrieval of past cases to support Insulin Dependent Diabetes Mellitus patients therapy revision. This tool was designed for assisting physicians during periodical monitoring visits. Each case is represented through i) a collection of features that describe the patient's clinical state at the decision time, i.e. the control visit, ii) the decision taken in terms of therapy revision and iii) the outcome obtained on the metabolic control during the following monitoring period. A new case is first classified into a protypical monitoring situation, and then similar cases are retrieved and shown to the user. This tool is fully integrated in a Web-based distributed system for Diabetes Management, developed within in the EU project T-IDDM.
Explore the source record for details and available documents.
The low affinity receptor for IgE, CD23, is expressed on lymphocytes among other cell types. The purpose of the present study was to assess serum sCD23 levels and CD23 expression on peripheral blood mononuclear cells (PBMC) in people at increased risk of developing Type 1 diabetes mellitus and in diabetic patients. Serum sCD23 levels were significantly higher in first-degree relatives of Type 1 patients (median: 3.2 U ml(-1)) (p < 0.001) and in newly diagnosed (median: 3.3 U ml(-1)) (p < 0.001) and long-standing (median: 2.5 U ml(-1)) (p = 0.01) Type 1 diabetic patients than in controls (median: 1.2 U ml(-1)). Newly diagnosed patients showed higher levels than those with long-standing disease (p = 0.026). Moreover the percentage of B cells expressing CD23 were significantly higher in first-degree relatives (median: 48.6%) (p < 0.001) and in newly diagnosed (median: 58%) (p < 0.001) and long-standing (median: 44.8%) (p = 0.03) Type 1 diabetic patients than in controls (median: 28.5%). The increased sCD23 levels and the increased number of cells expressing CD23 observed in subjects at increased risk of Type 1 diabetes and diabetic patients may be indicators of Th2 activity in Type 1 diabetes.
1. Autonomic abnormalities are frequent in adult patients with diabetes mellitus and progress slowly; little is known about frequency and progression of autonomic abnormalities in childhood. 2. To assess whether autonomic abnormalities are already present in childhood, we evaluated the cardiovascular reflexes, the spectral analysis of spontaneous fluctuations in RR interval and blood pressure (low- and high-frequency), and the baroreflex sensitivity at rest, and after vagal (controlled breathing) and sympathetic activation (tilting) in 25 adolescents with Type I diabetes mellitus, aged 10-17 years, at baseline and after 18 months follow-up, and in 20 age- and sex-matched controls. 3. Cardiovascular reflexes were similar in both patients and controls. Similar significant changes in percentage low- and high-frequency (P < 0.005) from rest to tilting and to control breathing were observed in both patients and controls. The baroreflex sensitivity was also similar in patients and controls. Mild and non-systematic correlations were observed between autonomic tests and disease duration or metabolic control. After 18 months follow-up no changes were observed in any of the measured variables. Correlations with metabolic control remained unchanged. 4. These results indicate a substantial stability of cardiovascular autonomic function in childhood diabetes, and suggest that autonomic abnormalities are likely to develop at an older age.
Few data are available from follow-up studies on diabetic retinopathy in patients diagnosed with insulin-dependent (Type 1) diabetes mellitus in childhood and treated with conventional therapy. We report the results of conventional insulin therapy on development of diabetic retinopathy in 100 children and adolescents (47 females and 53 males), aged 8.3 +/- 3.5 (1.2-16.4) years at diagnosis of disease. Oral or intravenous fluorescein angiography was performed during a 3-19 year follow-up in all patients. Retinopathy was staged according to the criteria of the Italian Society of Diabetology (SID). During follow-up, retinopathy was observed in 28 patients (28%). At the end of follow-up, retinopathy was present in 23 patients and had disappeared in 5. Life-table analysis showed a median disease-free interval of 10.8 years. At 10 years from diagnosis the percentage of patients free of retinopathy was 66%. Poor metabolic control, age, and degree of pubertal development at diagnosis were the most important risk factors.
The study aimed to evaluate the immune response to a recombinant hepatitis B vaccine in young patients with insulin-dependent diabetes mellitus (IDDM), in view of reports of reduced efficacy in adults with IDDM. Sixty-five young people with IDDM, age 4.5 to 27.5 and diabetes duration 0.3 to 19 years and 174 age- and sex-matched healthy subjects were injected with a recombinant hepatitis B vaccine at 0, 1 and 6 months intramuscularly in the deltoid region. Three (4.6%) IDDM patients and 2 (1.1%) controls were non-responders (HBsAb titre, < 2 IU l-1) and 1 control was a low responder (HBsAb titre = 10 IU l-1). Among the 3 non-responder IDDM subjects, 2 had other autoimmune disease. Median HBsAb titre was similar in responding patients (120 IU l-1 and controls (125 IU l-1). There were no significant correlations between antibody titre and age, diabetes duration, HbA1c or insulin requirement. No association was found between HBsAb titre and any HLA genotype or the presence of microangiopathy. IDDM does not adversely affect the immune response to a recombinant hepatitis B vaccine in children, adolescents, and young adults, who can thus expect to benefit from its use in situations of risk of contracting hepatitis.
Explore the source record for details and available documents.