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Biomedical subjects

D Fedele

Publications and source records attributed to D Fedele.

At least 19 recordsLinked to original sources
PubMed2005

Lymphocyte subsets and cytokines in women with gestational diabetes mellitus and their newborn.

This study aimed to identify potential immunological markers for predicting type 1 diabetes in patients with gestational diabetes mellitus (GDM) and any immunological impairment in their newborn. In 62 GDM patients and 74 women with normal glucose tolerance (NGT), and their babies, we assessed total lymphocytes, T lymphocyte subsets CD3 and CD8 expressing T cell receptor (TCR) alpha/beta or gamma/delta, CD16 and CD19, pancreatic autoantibodies and cytokines (IL-5, IL-2, soluble receptor IL-2). At delivery, umbilical cord blood samples were taken for lymphocyte subpopulations and cytokine measurements. GDM mothers had higher levels of total lymphocytes, CD8 expressing TCR gamma/delta, and lower levels of CD3 expressing TCR alpha/beta than NGT controls. Insulin-treated GDM mothers had lower CD4 and CD4/CD8 ratios, and higher CD8 and IL-5 than diet-treated GDM or controls. Five women were positive for pancreatic autoantibodies, with lower CD4 (p<0.01) and CD4/CD8 ratios (p<0.05), and higher CD8 (p<0.03) and CD19 than GDM and control mothers negative for autoantibodies. GDM newborn had higher CD8 gamma/delta and lower CD16 than NGT babies. There were no significant differences in TNF-alpha concentrations in the cord blood obtained from the GDM and NGT newborn. In conclusion, GDM women and their newborn have lymphocyte subset impairments, which are more important in patients positive for autoantibodies and/or treated with insulin.

Autoantibodies↗
PubMed2005

A matrix-assisted laser desorption/ionization mass spectrometry study of the non-enzymatic glycation products of human globins in diabetes.

The molecular species present in globins from healthy and diabetic subjects with and without chronic complications have been analyzed by matrix-assisted laser desorption/ionization mass spectrometry. The technique demonstrated the presence of glycated and glyco-oxidated species of both alpha- and beta-globins. Their abundances show a good linear relationship with respect to HbA1c values and with the mean daily plasma glucose levels over the 6 weeks preceding the investigation. Interestingly, slightly different behaviour is observed in the data from patients with and without chronic complications; the plots of HbA1c vs. the abundance of glycated and glyco-oxidated species show different slopes and different intercepts with the y-axis. To investigate this aspect the mean abundances of glyco-oxidated species from healthy subjects and from diabetic patients with and without complications were calculated. Higher values were found for the two last sets of samples, but no significant difference was found between them. These data could indicate different individual proclivities to oxidation and/or different oxidation kinetics related to behavioural and environmental factors.

Aged↗
PubMed2005

Pentosidine plasma levels and relation with metabolic control in diabetic patients.

Levels of plasma pentosidine, a well-known AGE, were measured in type 2 diabetic patients in varying states of metabolic control to verify possible relationships between this parameter and traditional metabolic control parameters such as HbA1c and plasma glucose levels. At baseline, mean values of fasting plasma glucose, HbA1c and pentosidine were significantly higher in diabetic patients than those of controls, confirming patients' poor glycemic control. After ten months, patients with good metabolic control achieved showed near-normal HbA1c levels and reduced but not normalized pentosidine levels. Significant differences were found in the mean percentage decrease in the parameters. Regarding linear correlation, HbA1c levels only showed a positive relationship with plasma glucose values at baseline. Patients affected by chronic complications showed higher levels of pentosidine than those without complications. Thus, pentosidine plasma levels may be used to evaluate very long-term metabolic control in diabetic patients. In addition, a period of ten months of acceptable metabolic control is not enough to normalize pentosidine levels in diabetics, thus emphasizing the need for a longer period of improved metabolic control to reduce both this parameter and the burden of chronic diabetic complications.

Aged↗
PubMed2005

Advanced glycation end products/peptides: an in vivo investigation.

Advanced glycation end products/peptides (AGE/peptides) originate by in vivo enzymatic digestion of nonenzymatically glycated proteins, which are produced by reaction of glucose with primary amino groups present in the protein chain following the Maillard pattern. AGE/peptides are highly reactive species and can interact with tissue and circulating proteins, leading to tissue modification and impaired protein functionality. Serum levels of AGE/peptides are reported to be particularly high in diabetes (in terms of higher production) or in end-stage renal disease (in terms of accumulation). For these reasons, their structural identification is of high interest, giving information on their relationship with the pathological state and allowing the design of possible therapeutic interventions. We report here some preliminary results obtained by liquid chromatography/electrospray ionization/mass spectrometry (LC/ESI/MS) and matrix-assisted laser desorption ionization MS (MALDI-MS) investigations carried out on the low-molecular-weight serum peptide fraction from 10 healthy subjects, 10 patients with poorly controlled diabetes, and 10 patients with end-stage nephropathy.

Amines↗
PubMed2004

The complexity of non-enzymatic glycation product sets of human globins.

AIMS/HYPOTHESIS: Recently an individual variability in the relationships between mean blood glucose levels and HbA1c has been observed among diabetic patients. The aim of this study was to provide an accurate description and evaluation of glycated and glyco-oxidated globins from diabetic subjects and their relationship with HbA1c and plasma glucose values. METHODS: We studied 20 type 2 diabetic and 10 healthy subjects. Plasma samples were analysed by matrix-assisted laser desorption ionisation mass spectrometry. RESULTS: The presence of glycated and glyco-oxidated species of both alpha and beta globin was demonstrated. Values for these showed a good linear relationship with HbA1c values and the mean daily plasma glucose values for the 6 weeks preceding the investigation. Trends differed according to whether patients had chronic complications or not, differences being seen in the slopes of the plots relating HbA1c to the abundance of glycated and glyco-oxidated species. CONCLUSIONS/INTERPRETATION: The data obtained are consistent with the concept that individuals have a different individual proclivity for oxidation and/or that different oxidation kinetics are related to behavioural and environmental factors. Our data are thus relevant to the analysis of phenotype differences in diabetic patients.

Aged↗
PubMed2003

Analysis of outcome of pregnancy in type 1 diabetics treated with insulin pump or conventional insulin therapy.

We evaluated the outcome of pregnancies followed between 1990 and 2000 in 93 women with type 1 diabetes, treated with conventional intensive insulin therapy (n=68) or continuous subcutaneous insulin infusion (n=25). We evaluated metabolic control (fasting and 1-hour post-prandial plasma glucose and HbA1c levels), spontaneous or induced abortions, time and mode of delivery, maternal outcome (pregnancy-induced hypertension, preeclampsia, placental insufficiency, hydramnios, hypoglycemic coma, ketoacidosis) and fetal outcome (weight, hypoglycemia, hypocalcemia, hyperbilirubinemia, fetal distress, asphyxia, hyaline membrane disease, polycythemia, shoulder dystocia, malformations). Patients treated with insulin pump more frequently had background retinopathy and clinical neuropathy. No significant differences were observed between the two groups in metabolic control and maternal outcome. Glycemic control, non-optimal in the prepregnancy state, improved significantly during pregnancy, as shown by the progressive reduction in HbA1c levels. As regards fetal outcome, no differences were observed between the two groups in morbidity and especially in malformation rate. Patients with malformed babies did not have optimal metabolic control at conception. Thus, maternal and perinatal outcomes were comparable in patients treated with insulin pump and continuous subcutaneous insulin therapy, and depended on metabolic control. In patients in higher White's class and with more unstable glycemia, we achieved metabolic control and outcomes comparable with those of women of lower White's class and more stable glycemic values using the insulin pump. Our data suggest that insulin pump therapy is useful in problematic, complicated cases of women who want a baby.

Adult↗
PubMed2003

Plasma lipoproteins, apoproteins and cardiovascular disease in type 2 diabetic patients. A nine-year follow-up study.

BACKGROUND AND AIM: To evaluate the role of lipoprotein abnormalities as risk factors for macroangiopathy in Type 2 diabetes. METHODS AND RESULTS: This prospective nine-year follow-up study involved 113 Type 2 diabetic patients (50 men and 63 women, mean age 66.9 +/- 9.9 years), 37 of whom had clinical signs of coronary heart disease (CHD) and cerebrovascular disease (CVD) at baseline. During the follow-up, 32 patients died: 17 of CHD, five of CVD, and 10 of non-vascular causes. The patients who died because of vascular disease were more frequently smokers, and had baseline symptoms of vascular disease; they were also significantly different from the other patients insofar as they were older, and had higher fasting plasma glucose levels, lower fasting C-peptide levels, and lower apoprotein (apo) AII, apo CII, apo CIII and apo E levels. Univariate analysis showed that baseline symptoms of vascular disease, current smoking, age, high fasting plasma glucose levels, low fasting C-peptide levels, and low apo AII, apo CII, apo CIII and apo E levels [but not cholesterol, triglyceride, high-density lipoprotein (HDL)-cholesterol or qualitative low-density lipoprotein or HDL abnormalities] were associated with cardiovascular mortality. Multivariate analysis showed that only age, smoking, glycated hemoglobin (HbA1c) and fasting C-peptide levels were significant independent determinants of macrovascular death. CONCLUSIONS: In Type 2 normolipidemic diabetic patients, only age, smoking, HbA1c and fasting C-peptide levels are independent vascular risk factors. The differences in apo concentrations between patients with and without vascular disease may reflect qualitative abnormalities in plasma lipoproteins related to vascular disease.

Age Factors↗
PubMed2003

Alternative site blood glucose testing: a multicenter study.

The aim of this study was to compare glucose measurements between fingertip and forearm using the blood glucose (BG) monitoring system One Touch Ultra (LifeScan), an electrochemical sensor that requires only a very small drop of blood (1 microL). Patients with type 1 or type 2 diabetes were identified in five outpatient diabetes clinics. Participants were requested to use the One Touch Ultra at home for 1 week for the measurement of BG levels from both sites. Patients filled in a questionnaire about their experience with testing blood samples from fingertip and forearm. The agreement between the measurements from the two sites was assessed using linear regression analysis, mean absolute relative error (MARE), the Bland-Altman method, and Error Grid Analysis (EGA). Overall, 112 patients were recruited, of whom 58% had type 1 diabetes. Linear regression analysis showed an intercept of 17.7, statistically different from 0 (p<0.0001). The slope was 0.956, and the Pearson correlation coefficient was 0.95. A MARE of 12.1% (SD=11.8%) was obtained, with a greater deviation of the forearm values from the fingertip ones in the hypoglycemic range (MARE=22.3%; SD=21.7%). The Bland-Altman bias plot showed a mean bias of 10.2 mg/dL (SD=23.1), with no correlation between mean difference and average BG levels (r=0.02). The EGA showed that 89.2% of the values fell in zone A, 10.4% in zone B, and 0.4% in zone C. The vast majority of patients (71%) declared that the collection of blood from the forearm caused no pain or less pain than the traditional site. Only 17% of the patients declared that it was impossible to obtain any blood from the forearm, while 63% reported with satisfaction that the quantity requested was small. At the end of the study period, 32% of the participants indicated the forearm as the preferred test site. Alternative site testing on the arm, with a BG meter that requires only a very small drop of blood, is feasible and reliable under routine clinical conditions. When testing with the express purpose of detecting hypoglycemia, the finger still remains the recommended test site.

Adolescent↗
PubMed2002

Non-enzymatic glycation of IgG: an in vivo study.

The IgG glycation level of 30 healthy subjects and 60 type 2 diabetic patients with different degrees of metabolic control was evaluated by matrix-assisted laser desorption ionization mass spectrometry, a technique allowing the determination of mass increase of the IgG molecule. When applied to the digested mixture obtained by the action of papain on the plasma protein fraction, the same method established the mass increase of Fab and Fc fragments of IgG; for the former, a higher mass increase was found, possibly explained by its high reactivity to glucose. Experimental results were confirmed by molecular modeling calculations. Results suggest that the immunodeficiency observed in diabetic patients may be due to the inhibition of molecular recognition between antibody and antigen as a result of a change in functionality of the modified Fab fragment of IgG.

Aged↗
PubMed2002

Low frequency of autoantibodies to islet cell, glutamic acid decarboxylase, and second-islet antigen in patients with gestational diabetes mellitus: a follow-up study.

The aim of the study was to determine the frequency of patients with gestational diabetes mellitus (GDM) who have serological markers typical of autoimmune type 1 DM. The specific pancreatic markers, ICAs, glutamic decarboxylase (GADAbs), and second islet antigen (IA2Abs), were measured in 70 women with GDM during the pregnancy and after delivery. ICAs were measured by indirect immunofluorescence and GADAbs and IA2Abs were determined by a radiobinding assay with recombinant antigens. On entering the study, 1 of 70 (1.4%) patients was positive for both ICAs (80 JDF-U) and GADAbs (167 U/mL), while another (1.4%) was positive for ICAs (40 JDF-U). None of the patients was positive for IA2Abs. During follow-up, positivity was maintained unchanged in the two positive patients. Four previously negative patients had seroconversion: one for both ICAs (20 JDF-U) and GADAbs (49.3 U/mL) and the other three for GADAbs (1.8, 1.4, and 15.3 U/mL, respectively). The IA2Abs remained negative in all patients. Overall, during the observation period 6 of 70 (8.6%) patients had or developed autoantibodies against endocrine pancreas. During follow-up 15 patients developed clinical DM (10 type 2, 5 type 1) and 7 demonstrated impaired glucose tolerance (IGT) after OGTT. No correlations were demonstrated between the immunological patterns and the evolution in DM. In patients with GDM, the frequency of pancreatic autoantibodies varies during the pregnancy and after delivery, but a small subgroup of patients bearing these markers is identifiable. GDM is a complex syndrome, constituted by different types of diabetes mellitus where the autoimmune form is very rare.

Adult↗
PubMed2001

Advanced glycation end products: a highly complex set of biologically relevant compounds detected by mass spectrometry.

Structural information on 'AGE-peptides,' a class of substances belonging to advanced glycation end products (AGE) and originating by proteolysis of glycated proteins, was gained through various analytical approaches on the mixture produced by proteinase K digestion of in vitro glycated bovine serum albumin. Both matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and high-performance liquid chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS) were employed, and the results were compared with those from conventional spectroscopic methods (UV, fluorescence, gel permeation). The data acquired by the various techniques all depict the digestion mixtures as highly complex, with components exhibiting molecular mass in the range 300-3500 Da. In the analysis of HPLC/ESI-MS data, identification of AGE-peptides was facilitated by 3D mapping. Structural information was gained by means of multiple mass spectrometric experiments.

Animals↗
PubMed2001

Cigarette smoking: a risk factor for erectile dysfunction in diabetics.

OBJECTIVES: Diabetes is one of the systemic disorders most frequently associated with erectile dysfunction (ED). An extensive literature documents well the relationship between ED and several factors related to diabetic pathology, but the role of risk factors mainly related to life-style, e.g. cigarette smoking, is still not defined. METHODS: Eligible for the study were men aged 20-70 years with a diagnosis of insulin-dependent (type 1---IDDM) or non-insulin-dependent (type 2--NIDDM) diabetes who were observed on randomly selected days in 178 diabetes centers in Italy. ED was defined as a failure to achieve and maintain an erection sufficient for satisfactory sexual performance. RESULTS: The study population consisted of 9,670 diabetic men. Of these 2,962 (30%) were never smokers, 2,877 (30%) current smokers and 3,831 (40%) ex-smokers. After taking into account the effect of age, the odds ratios of ED in comparison with never smokers was 1.4 (95% confidence interval 1.3-1.6) for smokers and 1.5 (95% confidence interval 1.3-1.6) for ex-smokers. Duration and intensity of the smoking habit was associated with an increased risk of ED. Among ex-smokers, the risk of ED significantly decreased; with increase in the number of years since the patient quit smoking. CONCLUSION: The study offers an assessment of the association between smoking habit and ED and its potential interaction with other risk factors in diabetic men.

Adult↗
PubMed2001

Incidence of erectile dysfunction in Italian men with diabetes.

PURPOSE: We determined the incidence of erectile dysfunction in Italian men with diabetes. MATERIALS AND METHODS: We estimated the incidence of erectile dysfunction, defined as failure to achieve and maintain erection sufficient for satisfactory sexual performance, after 2.8 years of followup in 1,010 men enrolled for a prevalence study of erectile dysfunction in diabetes. RESULTS: Of the 1,010 men 192 (19%) complained of erectile dysfunction. The crude incidence rate of erectile dysfunction was 68 cases per 1,000 person-years (95% confidence interval 59 to 77). The incidence of erectile dysfunction increased with increasing age (10-fold higher for ages 70 to 79 than for 19 to 29 years), duration of diabetes (1.6-fold higher a history of 11 years or greater than for less than 5) and deteriorating metabolic control (1.7-fold higher for hemoglobin A1c greater than 9% than less than 7.5%). Moreover, it was higher in type 2 than in type 1 diabetes (74 versus 45 cases per 1,000 person-years). The relative risk was 1.75, 2.02, 1.97, 1.16, 1.86, 3.79 and 1.52 for associated obliterative arterial disease of the lower legs, ischemic heart disease, renal disease, autonomic neuropathy, sensitive and motor neuropathy, diabetic foot and retinal disease, respectively. Of the characteristics at study enrollment patient age, duration of diabetes, renal disease and hypertension were multivariate predictors of the erectile dysfunction 2.8 years later. CONCLUSIONS: The incidence of erectile dysfunction in Italian men with diabetes at a mean followup of 2.8 years was 68 cases per 1,000 person-years, more than 2-fold that in the Massachusetts Male Aging Study of the general population. The knowledge of this incidence should promote specific preventive and therapeutic interventions for erectile dysfunction in men with diabetes.

Adult↗