L. Mughini

Evidence by magnetic resonance imaging of cerebral alterations of atrophy type in young insulin-dependent diabetic patients

Aim of this study was to investigate a) if through Magnetic Resonance Imaging (MRI) it was possible to reveal cerebral alterations in patients with insulin-dependent diabetes mellitus (IDDM); b) if there was any correlation with hypoglycemic episodes, glycometabolic control, microvascular alterations and diabetic peripheral neuropathy. For this purpose ten IDDM patients under treatment with human insulin, aged 19–30 yr with the disease, the duration being from 1 to 19 yr, were investigated by MRI using a Philips Gyroscan. Spin Echo sequences were used with images in T1 T2 in sagittal and axial planes. To measure the ventricular dilatation the cerebroventricular index (CVI) was evaluated. The MRI has put in evidence in 7/10 patients a dilatation in the lateral ventricles and subarachnoidal spaces of the cerebral vault and the cerebellum clearly due to cerebral atrophy. The CVI mean values (34.78±2.92) were statistically (p<0.001) higher in diabetic patients respect to control subjects (CVI mean values 27.5±1.58). These alterations did not present clear correlations with the degree of glycometabolic control, duration of disease, number of symptomatic hypoglycemic episodes and threshold for hypoglycemic symptoms, retinal microvascular alterations, microalbuminuria, diabetic peripheral neuropathy. The clinical or functional relevance of CVI changes and the exact pathogenic mechanism remains to be clarified.

Paradoxical Antidiabetogenic Effect of γ-Interferon in DP-BB Rats

Previous studies have shown that anti-γ-interferon (IFN-γ) antibody reduces the frequency of autoimmune IDDM in the DP-BB rat. We tested the effects of systemically administered recombinant rat IFN-γ in both DP-BB and DR-BB rats. Unexpectedly, IFN-γ markedly reduced the incidence of IDDM as compared with control rats when administered six times per week at a dosage of 280,000 U between ages 30-35 to 105 days or ages 60-64 to 105 days. A lower dosage (28,000 U on alternate days) was also protective when administered to DP-BB rats between birth and age 60 days. However, long-lasting protection against IDDM development over the 1-year study period was achieved only by the highest dosage of IFN-γ administered from age 30 to 105 days. Ex vivo production of tumor necrosis factor-a from splenic lymphoid cells (SLCs) and peritoneal macrophages of the rats treated with IFN-γ was comparable with that of controls; however, SLCs from the IFN-γ-treated animals secreted lower amounts of IFN-γ after stimulation with concanavalin A. IFN-γ treatment also markedly reduced the frequency of phenotypically activated SLC-expressing class II antigens and interleukin-2 receptor. Finally, in agreement with the observed antidiabetogenic effects, exogenously administered IFN-γ induced neither insulitis nor IDDM development in DR-BB rats, a subline of DP-BB rats in which autoimmune diabetes rarely occurs spontaneously but can be induced by administration of polyinosinic-polycytidilic acid.

FK-506 prevents diabetes in diabetes-prone BB/Wor rats

The effect of the immunosuppressant FK-506 on the development of diabetes in BB/Wor rats was investigated. Using a treatment schedule (25 micrograms i.m. from day 27 to 120), not associated with detectable general ill effects, this drug was found to completely inhibit the appearance hyperglycemia and to reduce the histological signs of pancreatic insulitis. The treatment was also able to reduce the percentages of Ia+ T-lymphocytes and to block the appearance of detectable serum levels of gamma interferon (IFN).

No Important Differences in Glycaemic Responses to Common Fruits in Type 2 Diabetic Patients

The aim of this study was to determine the glycaemic indices (GIs), peak incremental indices (PI), and time of peak increment (TPI) of eight kinds of fruits and their relationship with the type and amount of simple sugars directly assayed in the fruits. Sixty‐one type 2 diabetic patients randomized into eight groups—one for each category of fruit—participated in the study. GIs consisted of the following: pears = 60 ± 4.9; apples = 63 ± 8.3; oranges = 68 ± 6.5; grapes = 70 ± 7.5; plums = 75 ± 8.4; peaches = 80 ± 7.4; apricots = 82 ± 9.1; bananas = 83 ± 8.5. The PI values (mmol l−1) were the following: grapes = 2.52 ± 0.26; apples = 3.13 ± 0.75; pears = 3.48 ± 0.55; oranges = 4.02 ± 0.42; peaches = 4.07 ± 0.38; apricots = 4.08 ± 0.47; plums = 4.2 ± 0.45; bananas = 4.45 ± 0.39. There was no statistical differences in GI, and PI, within the different fruits. TPI of grapes (43.3 ± 5.2 min), oranges (45 ± 5.6 min), and peaches (45 ± 5.6 min) were statistical different (p < 0.01) in respect to apricots (81.4 ± 5.5 min). GIs were positively correlated with total glucose contained in the fruits (p < 0.05) and with PI (p < 0.0002); negatively with fructose both free (p < 0.02) and total (sum of free and present in sucrose (p < 0.05). On the basis of these findings, there is unlikely to be a difference of biological importance related to GI and PI of fruits, whereas the significance of TPI remains still to be evaluated.

Effects of synthetic salmon calcitonin administration on gastrin, immunoreactive insulin and growth hormone release after protein meal in uremic patients

Recent studies indicate that calcitonin inhibits, in man, the secretion of several hormones such as gastrin, insulin, growth hormone. There are no reports about this effect in uremic patients in which frequently calcitonin, gastrin, growth hormone, and insulin response to glucose administration is increased. A comparative study of the effects of synthetic salmon calcitonin infusion (50 U iv) on gastrin, growth hormone and insulin release after protein meal (250 g of boiled lean beef) in 10 uremic patients undergoing hemodialysis and in 10 normal subjects was performed. Insulin and growth hormone response to protein meal was inhibited by calcitonin both in normal and uremic subjects. Gastrin response instead was inhibited only in normal subjects. These findings indicate that in uremic patients the inhibitory effect of calcitonin on insulin and growth hormone secretion is still present. The lack of evident inhibitory effect on gastrin release could be related to persistent hypergastrinemia because of the increased half life of the hormone which could mask acute changes of secretion.

Protection from Experimental Autoimmune Thyroiditis in CBA Mice with the Novel Immunosuppressant Deoxyspergualin

The effects of the novel immunosuppressant Deoxyspergualin (DSP) on the development of experimental autoimmune thyroiditis (EAT) in CBA mice were studied. For EAT induction, the mice were immunized with 100 μg of porcine thyroglobulin (p Tg) emulsified in CFA on day 0 and in IFA, for boosting, on day 14. Twenty‐eight days after primary immunization, histological and serological signs of EAT occurred in control mice treated with PBS which showed marked lymphoid infiltration of the thyroid glands along with increased serum titres of anti‐pTg antibodies. Development of both these EAT features was significantly suppressed when the mice were treated with 2.5 mg/kg body weight DSP, given daily, five times a week, from day —2 to day + 28 after immunization. The effect appeared to be dose‐dependent and DSP was ineffective when given under the same experimental conditions at the dose of 0.5 mg/kg body weight. No DSP‐toxic effects could be observed during the experiment. These results provide further evidence for the powerful immunosuppressive properties of DSP and suggest that this drug may be used in the treatment of autoimmune thyroid diseases and other T‐cell mediated autoimmune disorders in humans.

Miscibility of semisynthetic human ultralente insulin with short-acting insulin in insulin-dependent diabetic patients

SummaryIn 15 insulin dependent diabetics (IDDM), treated with human monocomponent insulin, the absorption of Actrapid HM mixed with Ultratard HM was evaluated. Thirty U of Ultratard HM and 10 U of Actrapid HM were injected separately or together immediately after mixing. Free insulin and plasma glucose (PG) were measured four hours after the administration. Free insulin levels were significantly higher after 15 (2p<0.01), 60 (2p<0.05) and 90 min (2p<0.005) when the two insulins were injected separately. PG values were significantly lower (2p<0.05) (7.63±4.06 mmol/1) at 120 min when the two insulins were injected separately compared to the mixture (9.45±4.22 mmol/l). In conclusion, mixing Ultratard HM and Actrapid HM 3:1, we observed a decrease of early Actrapid absorption and a slower lowering of PG values.