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Biomedical subjects

U Di Mario

Publications and source records attributed to U Di Mario.

157 records · Page 9Linked to original sources
PubMedDate not supplied

Metformin decreases platelet superoxide anion production in diabetic patients.

BACKGROUND: Patients with type 2 diabetes mellitus are usually treated with oral antidiabetic agents but it is still not known whether these drugs have antioxidant effects in humans. METHODS: We studied 60 patients with type 2 diabetes mellitus, divided into three groups on the basis of hypoglycaemic treatment (Group A: metformin, Group B: glibenclamide, Group C: diet). All patients were followed for at least 1 year. The three subgroups had similar clinical characteristics. Twenty healthy subjects, of comparable sex and age, were enrolled as controls. In each subject, platelet production of superoxide anion (O(2)(-)) elicited by collagen, was determined by lucigenin assay. RESULTS: Patients with diabetes had higher platelet O(2)(-) production than controls; no correlation was observed between blood glucose and platelet O(2)(-) production. Group A patients had platelet O(2)(-) production similar to that of healthy subjects but lower than Group B and Group C patients. CONCLUSION: The present findings suggest an in vivo antioxidant activity of metformin and warrant prospective studies to further explore this hypothesis.

Antioxidants↗
PubMedDate not supplied

Genetic prediction of type 1 diabetes in a population with low frequency of HLA risk genotypes and low incidence of the disease (the DIABFIN study).

BACKGROUND: To develop a sensitive, specific screening strategy for predicting genetic risk for type 1 diabetes mellitus (T1DM) in the low-incidence continental Italian population, and to define with this tool, a cohort of high-to-moderate risk infants for an immunological follow-up study aimed at identifying environmental risk factors for T1DM. METHODS: 4855 newborns in three regions of continental Italy were screened for T1DM HLA-DRB1-DQB1 risk genotypes using a reverse line blot typing method. Risk classification was based on odds ratios (OR) found in a preliminary case-control study (356 T1DM patients, 412 controls). Screening efficiency was optimized by allele subtyping. RESULTS: Screening for well-known T1DM susceptibility genotypes [DRB1*03/*04-DQB1*0302; DRB1*03/*03; DRB1*04/*04-DQB1*0302; DRB1*04-DQB1*0302/X where X is not equal to DRB1*03, DRB1*04-DQB1*0302, DQB1*0602 or DQB1*0603] was associated with <60% sensitivity due to their low frequencies in the general Italian population. Inclusion of an additional genotype from which protective DRB1 and DQB1 alleles had been excluded [DRB1*03/X degrees where DQB1 is not equal to *0301, *0503, *0602, or *0603 and X degrees not equal DRB1*03, DRB1*04-DQB1*0302 or DRB1*07] increased screening sensitivity to 75% (specificity: 85%). Among 4855 newborns, we have found the high-risk genotype [DRB1*03/*04-DQB1*0302; estimated absolute risk (AR) 1/23] to be present in only 0.9%. The moderate-risk genotypes were found in 13.8% of newborns (estimated AR 1/177). CONCLUSIONS: Risk classification must be tailored to the characteristics of the individual population, in particular, the allelic frequencies in the background population and T1DM prevalence. We have developed a screening strategy with good levels of sensitivity that should prove effective for use throughout the Italian peninsula.

Adult↗
PubMedDate not supplied

Cell-mediated immunity and immune complexes in the pathogenesis of type 1 (insulin-dependent) diabetes.

Evidence for a role of the immune system in the pathogenesis of insulin-dependent (Type 1) diabetes is now plentiful. In the light of the lymphocytic infiltration in the islets of Langerhans, different autoaggressive mechanisms have been suggested in the initiation of B-cell damage. Lymphocytes characterized by cytotoxic properties (K cells) and having receptors for the Fc of IgG are increased in newly diagnosed Type 1 diabetics. Circulating immune complexes are also raised in these patients at the time of clinical diagnosis and there is evidence that K cells bind immune complexes which can modulate the activity of these cells. Here we propose a possible interrelationship between K or Fc gamma receptor+ T lymphocytes and immune complexes which could have a 'key' role in the mechanism of activation of cell-mediated immunity towards B-cells.

Antigen-Antibody Complex↗
PubMedDate not supplied

Early complications in type 1 diabetes: central nervous system alterations preceded kidney abnormalities.

Abnormalities of the central nervous system (CNS), as discerned by neuroelectrophysiological studies, and an impaired, charge-related, differential filtration of protein at kidney level as evaluated by selective protein clearance, have recently been shown in diabetes of short duration and without any apparent complication. In order to explore the time of appearance and possible correlations, CNS and kidney abnormalities have been evaluated in parallel both in short-term and long-standing type 1 diabetic subjects. Two groups of patients were studied: Group 1 (no. 15), with no previously known clinical sign of complications and less than 5 years from diagnosis; Group 2 (no. 15) with more than 10 years of disease and with or without clinical signs of diabetic complications. Twenty age and sex comparable normal subjects were included in the study (Group 3). Short-latency multimodal evoked potentials (visual-VEP, brainstem auditory-BAEP, median and tibial somatosensory m- and t-SEP) and charge and/or size selective protein clearances (albumin, anionic immunoglobulins, neutral/cationic immunoglobulins) were evaluated. In Group 1, 27% of patients showed neurophysiological abnormalities (P < 0.05 vs. Group 3) while one showed proteinuria. In Group 2, 60% of patients showed electrophysiological changes (P < 0.0001 vs. Group 3) while 67% showed abnormal charge or size selective proteinuria (P < 0.0001 vs. controls) with a significant association between the abnormalities of CNS and of charge selective proteinuria (P < 0.05). Thus, CNS abnormalities may be detected even in patients with diabetes of short duration and are later associated with subclinical kidney abnormalities. These findings stress the value of the multimodal evoked potential evaluation as a sensitive and early diagnostic approach to the study of diabetic complications.

Adult↗
PubMedDate not supplied

The selective elimination of anionic immunoglobulins as a parameter of kidney damage in diabetes and diabetic pregnancy.

IgG1 and IgG4 have similar molecular weights but differ in pH (about 9 and 4.6, respectively). Their different rates of excretion in the urine of diabetic patients may indicate an impairment of charge selectivity in the kidney filter. Working on this hypothesis, a sensitive new ELISA for the detection of urinary IgG4 has been developed. This method can detect less than 1 ng/ml of this immunoglobulin; total IgG was detected by a RIA method developed by our laboratory. Twenty-eight Type I diabetic patients with or without clinical nephropathy were included in a cross-sectional study. An additional seven diabetic patients were followed over time, and eight diabetic pregnant women were studied during the different trimesters of pregnancy. Whereas both IgG4 and total IgG values were increased in clinically nephropathic patients, levels of IgG4, but not IgG1-3, were enhanced in patients without clinical nephropathy. In the latter group as well, IgG4-positive patients were microalbuminuric; all but one of the remaining patients were IgG4 and albumin negative. There was no significant variation in IgG4 values with time on repeated samples. The increased glomerular filtration rate in diabetic pregnancy did not significantly modify the levels of IgG4 in the urine. These results are in accordance with a selective excretion of this medium to large sized anionic protein (IgG4) in incipient (or stage III) diabetic nephropathy. Urinary IgG4 could be an additional useful marker when studying diabetic patients with early and pre-clinical stages of diabetic nephropathy.

Adolescent↗
PubMedDate not supplied

Formation and ways of detecting advanced glycation end-products in isolated human glomerular basement membrane and human serum albumin nonenzymatically glycated in vitro.

The formation of advanced glycation end-products (AGE) was investigated in samples of isolated human glomerular basement membrane (hGBM) and human serum albumin (hSA) which had been nonenzymatically glycated in vitro. In order to measure AGE, two methods which differ in principle--the standard spectrofluorescence technique and the spectrophotometric diazonium salt reaction--have been used and compared. Samples of finely homogenized hGBM and hSA were incubated for 10 days in buffer containing 500 mmol/L (9 x 10(3) mg%) and 100 mmol/L (1.8 X 10(3) mg%) D-glucose respectively. At the end of the incubation period, the ambient glucose was removed and the samples were incubated for a further 10 days in glucose-free buffer. During this time, loosely bound sugar was released into the buffer; at the end of the incubation, the emission fluorescence at 440 nm (following continuous excitation at 370 nm) and the absorbance at 492 nm of the glycated hGBM and hSA samples were measured and found to be significantly increased by comparison with native samples (1-way ANOVA: p less than 0.05 with both techniques). Comparison of the two techniques used for AGE detection showed a positive linear correlation (Pearson's correlation coefficient r = 0.714; n = 8; p = 0.02). The released glucose probably originates from reversal of the Schiff base (the first and reversible step of the nonenzymatic glycation reaction), whereas fluorescence and photometric findings prove the presence of stable AGE on both hGBM and hSA. It is concluded that AGE can indeed be formed and detected by two different methods in hGBM (and hSA) subjected to nonenzymatic glycation in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Basement Membrane↗
PubMedDate not supplied

Immunogenicity of biosynthetic human insulin. Humoral immune response in diabetic patients beginning insulin treatment and in patients previously treated with other insulins.

The immunogenicity of biosynthetic human insulin (BHI) was studied in diabetic patients who had never received insulin treatment (Study A) and in diabetic patients who had already been treated with monocomponent insulin (Study B). The results of both studies were compared to matched control groups receiving other forms of insulin treatment. Blood samples obtained were tested for anti-insulin antibodies and circulating immune complexes using two different methods. After six months of treatment, the values of anti-insulin antibodies in those patients in Study A who were treated with BHI were significantly lower than those observed in control patients treated with monocomponent (P less than 0.02) or conventional insulin (P less than 0.001). At the sixth month of Study A no significant difference in the percentage of circulating immune complex positivity was seen between the three groups. In Study B no significant difference in the values of insulin antibodies or immune complexes was observed between patients who were switched to BHI and those who continued monocomponent insulin. No side effects were observed. The data show that the immunogenicity of BHI is even lower than that of monocomponent insulin.

Adolescent↗
PubMedDate not supplied

Semisynthetic human insulin: biologic and immunologic activity in newly treated diabetic subjects during a six-month follow-up.

Biologic and immunogenic activities of semisynthetic human monocomponent insulins were examined in insulin-dependent diabetic patients (group 1). Patients treated with porcine monocomponent (group 2) and conventional (group 3) insulins were studied for control purposes. The patients were examined before the beginning of insulin treatment and for a 6-mo follow-up period. The data collected during the study show that insulin antibody levels were significantly lower in group 1 than in groups 2 and 3. Furthermore, the prevalence of immune complexes assays with the C1q solid phase technique failed to reveal any differences between the three groups. When the conglutinin binding test was used, the prevalence of immune complexes showed a slight but not significant reduction in group 1 and a significant increase in group 3. The metabolic control was similar in the three groups during follow-up and the insulin requirement was lower, but not significantly, in group 1 than in groups 2 and 3. These data suggest that with human monocomponent insulins equivalent glycemic control may be achieved at similar doses than those required with porcine monocomponent insulins. Furthermore, human insulin is the least immunogenic of the present available insulins.

Adult↗
PubMedDate not supplied

[Prevalence of obesity in adolescence].

PURPOSE: A clinical epidemiological research was conducted in Sardinia on a sample of hig school students to survey the preminence of obesity and overweight during adolescence. PATIENTS AND METHODS: 304 normal subjects were examined, 161 males and 143 females ranging between 16 and 18 years of age. For each subject the index of body mass was considered then compared to the standard values of population using Hamil schedules. RESULTS: The survey revealed a normal weight in mostly of the teen-agers. Obesity was observed however in 23.6% of males and in 5.6% of females on what was seen the percentage of overweight or excessively fat subjects is below the percentage of underweight teen-agers (21% of males and 43% of females). CONCLUSIONS: This difference could be considered the proof of a particular adolescential attitude that seen as a positive aim and is identified with social acceptance and sexual attraction especially among girls. This is confirmed by the fact that when questioned a great number of teen-agers admitted they were or they had been on a diet to lo lose weight.

Adolescent↗