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Biomedical subjects

G M Nardelli

Publications and source records attributed to G M Nardelli.

At least 19 recordsLinked to original sources

In search of predictive markers of remission from insulin dependence in type 1 diabetes: a preliminary report.

We studied 18 newly diagnosed diabetic patients (8 males and 10 females, aged 18-26 years, within 10-120 days from the onset of symptoms) who were submitted for 15 days to intensive insulin therapy performed via subcutaneous insulin infusion (CSII). We investigated some metabolic and immunological parameters in order to identify a possible marker to predict the selection of patients potentially more responsive to CSII treatment for the remission of type 1 diabetes. In accordance with the International Diabetes Immunology Group we considered clinical remission as being the withdrawal of insulin therapy for at least 3 months. In order to assess beta-cell function a fasting and post-prandial serum C-peptide, blood glucose and HbA1c were performed on all patients before, and 3 days after, the discontinuation of CSII. Islet cell antibodies were determined in all sera by indirect immunofluorescence. Analysis of T-lymphocyte subpopulations was carried out before starting the therapy. The following monoclonal antibodies were used: CD4, CD8, CD57, CD25, HLA-DR. The levels of C3 and C4 and serum IgG, IgA and IgM were also evaluated. After CSII, 11 of 18 patients showed remission. At the beginning of the study we observed no major difference in metabolic parameters between the two groups. Interestingly, the patients who exhibited remission presented a statistically higher percentage of positive cells for CD57, HLA-DR and CD25 surface antigens, significantly lower C4 levels and CD4/CD8 ratio and significantly higher IgG levels compared with patients who did not show any remission.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Extreme insulin resistance due to anti-insulin receptor antibodies: a direct demonstration of autoantibody secretion by peripheral lymphocytes.

A 59-year-old woman with systemic lupus erythematosus was found to have marked hyperglycemia, extreme insulin resistance and abnormally high plasma immunoreactive insulin. Her circulating erythrocytes displayed a dramatic decrease of 125I-labeled insulin binding. Both the whole serum and purified IgG fraction strongly inhibited the binding of radiolabeled insulin to control erythrocytes. These results suggested, although indirectly, the existence of antibodies to insulin receptors in the serum of the patient. To directly investigate this issue, we used an enzyme-linked solid-phase immunoassay which allows the detection and enumeration of lymphocytes secreting antibodies towards insulin receptors. Peroxidase-conjugated anti-human immunoglobulin is used to reveal the binding of antibodies to insulin receptor-coated dishes. We demonstrated that the patient's mononuclear cells, when briefly incubated in Petri dishes with partially purified insulin receptor, were able to secrete immunoglobulins of G class specifically directed to the antigen. Moreover, only a fraction of the whole population of anti-insulin receptor antibodies was directed towards the insulin binding region of the receptor, seemingly corresponding to the auto-antibodies detected with conventional binding-inhibition assay.

Antibody-Producing Cells↗

The influence of aging on the normal oral glucose tolerance.

381 glucose intake normal curves were studied according to the Diabetes Data Group new classification in healthy persons between 10 and 80 years in order to assess the influence of the age upon the normal glucose tolerance. Such an influence, which was evident in all the subjects, turned out to be more important in women with respect to me. In fact, males showed an increase, per decade, of about 1 mg/dl in fasting glycemic levels, of about 6 mg/dl at 60', of 4 mg/dl at 120', while in females there was an increase of about 2 mg/dl in fasting glicemic values, of about 6 mg/dl at 60' and of about 5 mg/dl at 120'. No meaningful correlation between age and insulinemic values was found at all considered points, either in males or in females. The reasons of the decreased glucose tolerance with aging and of its different behavior in the two sexes are discussed.

Adolescent↗

Erythrocyte cholesterol and red blood cells deformability in diabetes mellitus.

The study was designed to determine eventual correlation in diabetes mellitus between reduced erythrocyte deformability and red blood cells (RBC) cholesterol content. Significantly higher RBC cholesterol amount was found in 11 diabetics (IDDM) than in 13 controls of similar age (45 +/- 10 yrs) (1.30 mg ml-1 packed cells -1 +/- 0.15 SD vs 1.19 +/- 0.10 SD, p less than 0.05). Blood filterability values have been found significantly higher (p less than 0.025) in the diabetics (42.2 +/- 11.5 SD ml sec. -1) than in controls (33.5 +/- 6.0). Flow time of RBC filterability, measured in erythrocyte saline buffered suspension (40% Hct) in order to eliminate interferences from plasmatic factors, showed a closely correlation with RBC cholesterol content (r = 0.86 p less than 0.01). A significant inverse correlation between RBC cholesterol content and serum ApoA1-HDL levels was also observed (r = -0.58, p less than 0.05). Moreover ApoA1-HDL serum values were significantly (P less than 0.01) lower in diabetics (111.8 +/- 10.1 mg/dl) than in controls (126 +/- 6.6 mg/dl). Our data underline the possible involvement of augmented erythrocyte cholesterol in impairing the microhemologic competence of RBC in diabetes mellitus. A possible relation with lower ApoA1-HDL and lecithin-cholesterol-acyl-transferase (LCAT) is examined.

Adult↗

Pyruvate dehydrogenase activity in adipose tissue mitochondria from normal and obese humans.

Pyruvate-dehydrogenase, an enzymatic mitochondrial complex, exists in both inactive and active forms, insulin being the regulating factor of the transformation of a latter into the former. The basal (PDHb) and total (PDHt) activity of this enzyme in adipose tissue mitochondria from obese hyperinsulinemic humans has been found equal to 1014 +/- 459 SD mU respectively. These values are 250% higher than those found in normal subjects (403 +/- 76 SD and 575 +/- 142 SD respectively). Both in normal and obese subjects the PDHb/PDHt percent ratio was equal to about 70. These results show that insulin, undoubtedly hyperactive in obesity, by activating PDH can induce a major synthesis of fat, a high caloric density tissue.

Adipose Tissue↗

[Effect of phenethylbiguanide on the respiratory activity of liver mitochondria of rats treated with glucagon].

The effect of PEBG on respiration and oxidative phosphorilation (succinate as substrate) has been studied in liver mitochondria of rat treated with glucagon. The results obtained indicate that, while glucagon, as reported by others, induce a significant increase of respiration rate in state 3 (+ ADP), PEBG, at pharmachological dose, antagonizes this effect. The conclusion is that PEBG exertes its hypoglycemic activity by inhibiting the gluconeogenic reactions promoted by glucagon. This is strongly evident in diabetic or starwed conditions.

Animals↗

[Urinary excretion of catecholamines in obese subjects and in diabetics (author's transl)].

95 obese subjects, 40 diabetics and 22 normal controls were investigated. The weight of all obese subjects was at least 20% higher than the ideal weight. Catecholamine excretion was determined a few days after hospitalization to minimize the influence of environmental changes. Spectrofluorimetric estimation of adrenaline and noradrenaline in the urine was carried out according to the method of von Euler and Lihajko. Statistical analysis of the results showed a significant increase in both adrenaline and noradrenaline excretion in the group of obeses subjects compared with the diabetics. The increased catecholamine excretion may represent the response of the adrenal medulla to the stress of the disease. Such an increase may be responsible for perpheral insulin resistence and hence acts as a diabetogenic factor. The results obtained emphasize the influence of catecholamines on insulin responsiveness, possibly constituting a major contribution to the diabetic state.

Adrenal Medulla↗

Remission from insulin dependence induced by continuous subcutaneous insulin infusion (CSII) in type I, newly diagnosed diabetics: role of some hormonal and immunologic factors.

Optimal and early control of recent onset, type I diabetes by intensive insulin therapy has been reported to allow insulin withdrawal in about two thirds of subjects treated. We used continuous s.c. insulin infusion (CSII) in the attempt to induce a temporary remission of insulin dependence in 18 newly diagnosed young adult diabetics. After 10 days of optimized glycometabolic control, insulin infusion was stopped and patients were switched to glibenclamide (15 mg/die) plus metformin (1 g/die). Diabetics were considered in remission of insulin dependence when their metabolic control fulfilled the following criteria for at least 3 months: absence of glycosuria, pre- and post-prandial blood glucose less than or equal to 120 and 180 mg/dl, respectively, HbA1c less than or equal to 7%. Insulin therapy could be discontinued for periods of over three months in 11 subjects (61%) and for as long as 18 months in one case. Insulin requirement during CSII was slightly higher in nonremitters (NR) than in remitters (R): 0.36-0.64 vs 0.26-0.41 U/kg/die. After 24 months from CSII, R still showed lower insulin requirement (0.35-0.42 U/kg/die) than NR (0.55-0.75 U/kg/die). Further, the role of some hormonal and immunologic factors was investigated. Plasma C-peptide and glucagon were measured, fasting and 2h after each meal, both on admission and immediately after CSII, when patients were switched to oral therapy. No difference in hormone levels could be detected on admission, whereas, after CSII, mean post-prandial increase of C-peptide over basal was significantly higher in R than in NR (1.18 +/- 0.37 vs 0.22 +/- 0.16 ng/ml, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗