M. Lunetta

Safety, efficacy, acceptability of a pre-filled insulin pen in diabetic patients over 60 years old

The aim of the study was to evaluate safety, efficacy and acceptability of a pre-filled insulin pen device (NovoLet) in diabetic patients over 60 years old already treated with insulin administered with conventional syringes. After a run-in period of 2 weeks, 60 patients participated in a randomized cross-over study with two 6-week treatment periods using the insulin pen or conventional syringes. Insulin regimens did not change during the study. Hypoglycaemic episodes did not differ significantly between both kinds of treatment and no severe hypoglycaemia was registered. HbAlc (%) was (mean +/- S.D.) 7.7 +/- 1.2 and 7.9 +/- 1.1 during pen and syringe treatment, respectively. Blood glucose profiles were similar during both treatment modalities except for pre-lunch blood glucose values (mmol/l) lower during pen treatment (8.7 +/- 2.9 vs. 9.2 +/- 2.7, P < 0.01). The insulin dose (U/day) was 31.9 +/- 8.9 (pen) and 32.3 +/- 9 (syringe). 54 patients found the functioning of the insulin pen easy to understand and preferred it for future treatment because the conditions of insulin administration are faster and easier than with conventional syringes. We concluded that the pre-filled insulin pen is safe, efficacious and is highly accepted in over 60 years old diabetic patients.

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.

Increased frequency of HCV and HBV infection in type 2 diabetic patients.

The aim of our study was to verify if the diabetic population can be considered at risk for HBV (B hepatitis virus) and/or HCV (C hepatitis virus) correlated viral hepatitis. We examined 1514 diabetic patients, 668 males and 846 females. In patients who had, on at least two occasions, pathological transaminase values (AST and/or ALT), the markers for HBV and HCV infection were determined. Of the 1514 patients studied, 295 (19.48%) had pathological values of ALT and /or AST. Among the hypertransaminase patients (295), 69 were not tested for the markers because they refused to give informed consent; of the remaining 226 patients, 54 were negative and 172 (76.6%) were positive for at least one of the hepatitis markers (HBV, HCV or both). Those who were anti-HCV positive were 115 (38.98%), of which 50 were also positive to hepatitis B (16.9%), while those positive only to the B markers were 57 (19.3%). If we compare the patients with positive markers (172) to the total number of diabetic patients studied (1514), we find that there is a hepatitis B and/or C prevalence of 11.36%, with no statistically significant difference between females (95/846, 11.23%) and males (77/668, 11.53%). The prevalence of only hepatitis C was 7.6%, while only hepatitis B was 7.1%. In conclusion, our study shows an increasing prevalence of hepatitis C and B, often associated, in type 2 diabetic patients that allows us to define them as a group at risk for viral hepatitis.

A simplified diagnostic test for ambulatory screening of peripheral diabetic neuropathy

The reliability and reproducibility of Michigan Neuropathy Screening Instrument (MNSI), a recently proposed simple test for ambulatory screening of peripheral diabetic neuropathy (PDN), was evaluated on 80 diabetic patients. MNSI was carried out by two diabetologists and repeated after a week. It consisted of the sum of scores varying from 0 to 1 for each abnormality revealed in foot appearance, achilles reflexes presence and vibratory threshold (VPT) by tuning fork (maximum score = 8). Then patients had to go to neurologist for PDN diagnosis by a quantitative neurological examination and electrophysiological evaluation, the so named Michigan Diabetic Neuropathy Score (MDNS) and the results compared with MNSI score according to one of the two observers. The inter-observer reproducibility of MNSI was 88.75% the within observer reproducibility was 95 and 94%, respectively, for each observer with good correlation between the two measurements (P < 0.001). The MNSI score of 2.5 as a cut-off appeared to be reliable for ambulatory screening of suspected PDN (false positive and false negative = 2.5%; specificity and sensitivity = 75% and 78.6%, respectively). In conclusion MNSI by using 2.5 score as cut-off may be considered a rapid, simple, reproducible and reliable test for rapid ambulatory screening of PDN from the diabetologists.

Prevention of Spontaneous Autoimmune Diabetes in Diabetes-Prone BB Rats by Prophylactic Treatment with Antirat Interferon-γ Antibody

The role of endogenous interferon-γ (IFNγ) in the development of insulin-dependent diabetes mellitus (IDDM) in diabetes-prone BB rats was evaluated. Several groups of these animals were treated under different experimental conditions with a purified polyclonal antibody (Ab), antirat IFNγ. The results show that when administered at doses of 100 or 200 μg/week from the 30/33th until the 105th day of age, the anti-IFNγ Ab reversibly reduced the incidence of IDDM compared to that in control rats treated with either irrelevant rabbit IgG or PBS. Moreover, when given up to the 105th day of age, these doses of anti-IFNγ Abs exerted comparable preventive effects regardless of whether application started as early as within 24 h after birth or at the end of the prediabetic period (e.g. 70/75 days). In contrast, under none of the above experimental conditions did larger doses of anti-IFNγ Ab (500 μg or 1 mg/week) exert antidiabetogenic effects in the BB rats. Apparently, this was due to the exuberant production of n...

Correlation between islet cell antibodies and anti-cytomegalovirus IgM and IgG antibodies in healthy first-degree relatives of type 1 (insulin-dependent) diabetic patients

To investigate whether cytomegalovirus (CMV) infection may be related to islet cell antibodies (ICA) production and/or to insulin-dependent diabetes mellitus (IDDM) development, we have analyzed the prevalence of anti-CMV, IgM, and IgG antibodies and of ICA in 80 healthy siblings of IDDM patients (HSIDDP) and in 60 control subjects with negative familiar anamnesis of IDDM. HSIDDP and controls were also typed for HLA-A-B-C and DR antigens. IgM and IgG anti-CMV were detected by an ELISA method, whereas the ICA assay was performed by standard indirect immunofluorescence on 5-microns unfixed sections of human pancreas. HLA-A-B and C antigens were studied by standard microlymphocytotoxicity; DR antigens were also studied by a standard microlymphocytotoxicity on a B-enriched lymphocyte population. Our results indicate a significant association (P less than 0.0001) between high titers of anti-CMV IgG antibodies and ICA in HSDIDDP, whereas no correlation was found between the presence of any HLA-A-B-C and DR antigens and the prevalence of anti-CMV IgM and IgG antibodies and/or ICA. Thus, these data may support the hypothesis that a chronic CMV infection may be associated with ICA production whereas other factors seem to be needed for the complete development of type 1 diabetes.

Increased urinary albumin excretion is a marker of risk for retinopathy and coronary heart disease in patients with type 2 diabetes mellitus

The prevalence of increased urinary albumin excretion (UAE) (micro- and macroalbuminuria) and its association with diabetic retinopathy (DR) (evaluated by fluorescent angiography), coronary heart disease (CHD), and various related risk factors were studied in 320 type 2 diabetic patients. In this subsample of type 2 diabetic patients, microalbuminuria was present in 15% of the patients; macroalbuminuria in 4.8%, CHD in 9.9%, DR in 53.4%, and arterial hypertension in 46%. UAE was independently related to CHD (P < 0.05), retinopathy (P < 0.001), hypertension (P < 0.001), and triglycerides (P < 0.02). We conclude that increased UAE is associated to a greater frequency of retinopathy and CHD in type 2 diabetic patients.

Long-term octreotide treatment reduced hyperinsulinemia, excess body weight and skin lesions in severe obesity with acanthosis nigricans

A boy affected by severe obesity (kg 117, Body Mass Index 37 kg/m2) and acanthosis nigricans, was treated with octreotide for 150 days (50 μg × three daily subcutaneous administrations). Before treatment the patient showed an exaggerated insulin (IRI) and C-peptide (CPR) response to a standard meal with a lowering in after-meal CPR/IRI molar ratio. During octreotide treatment both IRI and CPR response was reduced but CPR/IRI molar ratio rised after meal indicating an increase in hepatic insulin removal. Body weight and acanthosis nigricans were sharply reduced during treatment and the reduction was still maintained six months after the cessation of therapy. Furthermore, IRI and CPR response, as well as the behaviour of CPR/IRI molar ratio, remained within normal range. In conclusion long-term octreotide treatment has been able to correct hyperinsulinemia and to reduce body weight and acanthosis nigricans.

Enhanced percentage of CD5+ B lymphocytes in newly diagnosed IDDM patients

The percentage of CD5+ B lymphocytes, the prevalence of islet cell antibodies (ICA) and of anti-insulin autoantibodies (IAA) and HLA-A-B-C and DR antigens were studied in 32 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients, in 12 non-insulin-dependent diabetes mellitus (NIDDM) patients and in 12 healthy subjects. The percentage of CD5+ B lymphocytes ranged from 18% to 51.2% (mean 40.3 +/- 11%) in IDDM patients, whereas in NIDDM patients and in controls it ranged from 20% to 25.2%, (mean 21.3 +/- 4.1%) and from 16% to 24%, (mean 19.3 +/- 1.9%), respectively (P less than 0.01 vs. NIDDM patients and vs. controls). There was no correlation between a higher percentage of CD5+ B lymphocytes and the presence of ICA and/or IAA, and their titres, and/or of any HLA-A-B-C and DR antigens. Thus, an enhanced percentage of CD5+ B lymphocytes may be present in newly diagnosed IDDM patients; the possible role of this cell type in the pathogenesis of IDDM needs further investigation.

Effects of salmon calcitonin on blood glucose and insulin levels under basal conditions and after intravenous glucose load

A study of the effects of salmon calcitonin (sCT) infusion on blood sugar and serum insulin levels under basal conditions and after intravenous glucose load in normal subjects is reported. Under basal conditions, a 30 min infusion of sCT at approximately a rate of 1 U/min produced a highly significant increase in the blood sugar (p < 0.01) and a highly significant decrease in the serum insulin levels (p < 0.01). After intravenous glucose load, there was a decrease of the coefficient of glucose utilization and of the insulin response both of which were highly significant (p < 0.01).