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Biomedical subjects

D Fedele

Publications and source records attributed to D Fedele.

At least 37 records · Page 2Linked to original sources

Preprandial combination of lispro and NPH insulin improves overall blood glucose control in type 1 diabetic patients: a multicenter randomized crossover trial.

BACKGROUND AND AIM: While lispro insulin has been reported to lower postprandial blood glucose concentrations, less consistent effects have been shown for glycosylated hemoglobin (HbA1c) levels. Aim of this study was to determine whether pre-meal association of NPH, an intermediate-acting insulin, with lispro improves overall glycemic control in type 1 diabetic patients. METHODS AND RESULTS: Eighty-five type 1 diabetic patients were studied in a multicenter randomized comparative (human regular vs lispro insulin) crossover (3-month) study in which NPH insulin was given as a dinner or bedtime injection and at breakfast and lunch if necessary. The number of injections was kept constant: 42% and 58% of patients injected insulin 3 and 4 times per day, respectively. Fasting and preprandial blood glucose levels were similar, while postprandial levels improved after lispro compared to human regular insulin (breakfast: 8.28 +/- 2.39 vs 9.28 +/- 2.72 mmol/l; lunch: 8.33 +/- 2.67 vs 9.06 +/- 2.67 mmol/l, dinner: 8.06 +/- 2.72 vs 9.28 +/- 2.44 mmol/l, ANOVA: p = 0.003). HbA1c also improved after lispro: 8.1 +/- 0.9 vs 8.3 +/- 0.8%, p < 0.05. The rate of hypoglycemia was similar. Patients showed better acceptance of lispro treatment (p < 0.001). CONCLUSIONS: Lispro improves overall blood glucose control in type 1 diabetic patients without increasing the incidence of hypoglycemia. This can be achieved by an optimal combination of lispro insulin with NPH whenever the time intervals between meals are too long.

Adolescent↗

Management of erectile dysfunction in diabetic subjects: results from a survey of 400 diabetes centres in Italy.

We report the results of a survey on erectile dysfunction (ED) conducted in 400 Italian Diabetes Centres in 1998. A questionnaire consisting of 10 items was sent to the Centres recorded by the Italian Association of Diabetologists and the Italian Society of Diabetology; 400 Centres returned the completed questionnaire (58%). Forty-nine percent of the Centres declared that they investigated ED systematically but less than half of them (46%) had done it autonomously. The percentage of Centres performing intracavernous injection (ICI) was 84%. This maneuvre was most commonly performed by diabetologists (61%), followed by urologists (29%) and andrologists (18%) (categories are not mutually exclusive). ICI was also the most common type of treatment (85%), followed by oral (32%) and topic (7%) therapies (categories are not mutually exclusive). Slightly more than half of the interviewed Centres (51%) did not investigate ED routinely, attributing this to structural problems, lack of specific training and the availability of more specialised Centres as the main reasons for this. However, the majority of Centres expressed interest in managing ED. Among the available tests for ED, ICI was the most frequently employed. While most Centres seek the collaboration of external specialists to diagnose ED, the diabetologist is the physician who most frequently performs ICI. We conclude that Italian diabetologists need specific training to reach a greater degree of autonomy in the management of ED in their patients.

Community Health Centers↗

Antepartum and early postpartum predictors of type 2 diabetes development in women with gestational diabetes mellitus.

OBJECTIVES: This study aimed at identifying ante-partum and early post-partum (one year) clinical and metabolic characteristics capable of predicting the future development of type 2 diabetes in pregnant women of Mediterranea area affected by gestational diabetes mellitus (GDM). MATERIAL AND METHODS: Seventy GDM patients were evaluated: mean age during pregnancy, plasma glucose levels under OGTT (100 gr. glucose), fasting, 1-h post-prandial plasma glucose levels, HbA(1c) at the third trimester, gestational week of GDM diagnosis, insulin therapy, and weight gain were all taken into consideration. Some maternal risk factors such as pre-pregnancy BMI, and maternal and fetal outcome of index pregnancy were also assessed. One year after delivery in the same patients, BMI, fasting and 1-h post-prandial plasma glucose, plasma glucose and insulinemia under OGTT (75 gr. glucose) were measured. We focused our attention on women who presented type 2 diabetes 5 years after pregnancy or IGT and those who, one year after pregnancy, were normal. RESULTS: Five years after pregnancy 49 women were normal, 5 had developed type 1 diabetes and were not considered, 6 had developed IGT, and 10 type 2 diabetes. Analysis of variables during pregnancy showed that those variables predicting type 2 diabetes were pre-pregnancy BMI, gestational week of diagnosis, need for insulin therapy, obesity, and plasma glucose at 60' OGTT. Analysis of variables evaluated one year after pregnancy showed that BMI, fasting and post-prandial plasma glucose, plasma glucose at each point of the OGTT, and plasma insulin at 30' OGTT were predictive of the development of type 2 diabetes. Furthermore, age, post-partum fasting plasma glucose, and plasma glucose under OGTT post-partum were predictive of the development of IGT. Our data show for the first time that, also in a Caucasian Mediterranean population, markers of the future development of diabetes do exist, as reported in literature. They also stress the importance of correct identification of GDM patients, in order to screen those at greater risk of developing diabetes, for whom it is imperative to set up prevention programs.

Adult↗

Cigarette smoking is a risk factor for nephropathy and its progression in type 2 diabetes mellitus.

Cigarette smoking is a risk factor for diabetic nephropathy in Type 1 diabetes (T1DM); a few reports support this possibility in Type 2 diabetes (T2DM) as well. Since heterogeneity among populations could exist, we investigated the association of cigarette smoking and nephropathy, and progression of nephropathy in Italian T2DM patients. A retrospective study was conducted in 273 long-duration T2DM subjects with a 3-year follow-up in the out-patient clinic, and at least one access per year. Albumin excretion rate, serum creatinine, and a number of other parameters implicated in the development of diabetic renal disease were evaluated. Progression of nephropathy was defined as the passage from different stages of renal involvement (no renal derangement, microalbuminuria, proteinuric disease or severe nephropathy). At baseline, 13.2% of the subjects had microalbuminuria, and 3.7% proteinuric disease. Microalbuminuria and proteinuric disease were more frequent in actual smokers than in non- and former smokers (chi2=8.35; p=0.015). Progression of nephropathy was less common in non- and former smokers than in smokers (31 of 134, 23%, and 15 of 67, 22%, and 30 of 72, 42%, respectively; chi2=9.32;p=0.009). From logistic regression analysis, smoking (p=0.0012) emerged as the most important factor associated with progression of nephropathy, followed by packyears (p=0.011), HbA1c mean value at follow-up (p=0.024), and total cholesterol (p=0.038). In conclusion, cigarette smoking is a risk factor for progression of nephropathy also in Italian T2DM patients; reducing or quitting smoking should be part of the therapy or of the preventive measures in these patients and their relatives.

Aged↗

Evaluation of T-cell receptor CD3+ gamma delta in gestational diabetes mellitus.

Few studies have shown a significant increase of CD3+ T-cell receptor (TCR) gamma delta in the early phases of type 1 diabetes. We wished to determine if CD3+ TCR gamma delta is involved in the pathogenesis of gestational diabetes mellitus (GDM). We studied 29 GDM patients and 21 normal pregnant women. Lymphocyte subpopulations (CD3+ TCR alpha beta, CD3+ TCR gamma delta), islet cell antibodies (ICA), glutamic acid decarboxylase antibodies (GAD) and protein tyrosine phosphatase antibodies (IA2-Ab) were evaluated in all patients. The percentage of CD3+ TCR gamma delta was significantly higher in GDM women than in the control group (5.1 +/- 2.9% vs 3.7 +/- 1.7%; p < 0.05). No abnormalities of the other lymphocyte subpopulations were found. All subjects were negative for ICA; 2 GDM patients were positive for GAD, but no relationship was found between GAD positivity and CD3+ gamma delta levels in these 2 patients. Further follow-up studies of these patients are required to verify if the CD3+ TCR gamma delta receptor is a useful marker for diabetes development.

Adult↗

Evaluation of diagnostic reliability of DCA 2000 for rapid and simple monitoring of HbA1c.

The monitoring of diabetic patients by evaluating glycated protein levels is now widely accepted and performed. The microchromatographic version of the high performance liquid chromatography method is the technique most frequently used in clinical practice. The DCA 2000 instrument (Bayer Diagnostics, Milan, Italy), based on an immunochemical technique, has been proposed for the rapid and simple evaluation of HbAlc, using even capillary blood. We evaluated 171 subjects including 22 healthy volunteers, 78 type 2 diabetic patients with different degrees of metabolic control, 11 women affected by gestational diabetes mellitus (GDM), 6 patients with hyperlipemia, 38 patients with chronic renal failure, 13 diabetic patients with chronic renal failure, and 3 patients with hemoglobinopathies. The DCA 2000 model was compared with the Diamat HPLC system. Data from within-run imprecision studies showed excellent precision, for both DCA 2000 and the HPLC system. The correlation between the two different systems, as shown by other statistical evaluations, was good (y = 0.911x + 0.462, r = 0.923). Results from the control group and diabetic patients were used to compare the two methods. Values obtained using the DCA 2000 were significantly lower (p < 0.0001) than those obtained with the HPLC system, in both healthy subjects and diabetic patients. To detect possible interferences, selected samples were analyzed from patients with hyperlipemia, diabetes and chronic renal failure, and hemoglobinopathies. While in the case of hyperlipemia, an acceptable correlation coefficient between the two systems was confirmed (y = 1.047x - 1.236, r = 0.876), in the case of chronic renal failure the correlation turned out to be very low (y = 0.254x + 3.456, r = 0.203). Our results indicate that the DCA 2000 gives accurate and reliable results in the clinical field of interest.

Aged↗

Matrix-assisted laser desorption/ionization mass spectrometry, enzymatic digestion, and molecular modeling in the study of nonenzymatic glycation of IgG.

The glycation-induced functional change of immunoglobulins is of particular interest. The glycation levels of IgG in 10 healthy subjects and 20 diabetic patients with different degrees of metabolic control were studied by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. It reveals the number of glucose molecules that have condensed on the protein, which range from 1 to 5 for healthy subjects, from 5 to 9 for well controlled diabetic patients, and from 10 to 25 for poorly controlled ones. The identification of the most favored glycation sites has been obtained by MALDI analysis of standard and in vitro glycated IgG and plasma protein fraction of a healthy subject after digestion with papain, releasing Fab and Fc fragments of the molecule. Both experiments, as well as molecular modeling of the whole protein, confirm that the most of glucose molecules have condensed on the Fab fragment of IgG, suggesting that the immune deficiency observed in diabetic patients may be explained at the molecular level by a more effective glycation of the Fab fragment, thus inhibiting the process of molecular recognition between antibody and antigen.

Aged↗

Erectile dysfunction in type 1 and type 2 diabetics in Italy. On behalf of Gruppo Italiano Studio Deficit Erettile nei Diabetici.

BACKGROUND: Several studies reported data on the increased risk of erectile dysfunction (ED) in populations of diabetic men, but few presented data separately for Type 1 and Type 2 subjects. No comparison data for these diabetic subgroups are available with regard to risk factors for ED. METHODS: Eligible for the study were men aged 20-69 years with a diagnosis of insulin-dependent (Type 1) or non-insulin-dependent (Type 2) diabetes who were observed on randomly selected days in 178 diabetes centres in Italy. Erectile dysfunction was defined as a failure to achieve and maintain an erection sufficient for satisfactory sexual performance. RESULTS: The study population consisted of 1383 Type 1 and 8373 Type 2 men. The prevalence of ED increased with age for both groups. After taking into account the effect of age Type 2 men (37/100 men) tend to report ED less frequently than Type 1 men (51/100 men). A significant positive relationship was reported between ED and poor metabolic control and smoking for both Type 1 and Type 2 men, whereas high body mass index (BMI) increased only the risk of ED in Type 1 cases. CONCLUSIONS: The study offers a quantitative estimate of the prevalence of ED and its main risk factors in Type 1 and Type 2 diabetic subgroups.

Adult↗

Direct evaluation of glycated and glyco-oxidized globins by matrix-assisted laser desorption/ionization mass spectrometry.

Matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) has been applied to achieve a qualitative and quantitative evaluation of glycated globins on a wide number of healthy and diabetic subjects. The method allowed us to establish that both alpha- and beta-globins are glycated and that, in addition to simply glycated products, other species are detected. Investigations by different sample treatments and by analysis of the glycated beta-globin fraction obtained by preparative chromatography indicated that these species correspond to glyco-oxidized globins. Consequently MALDI-MS can be validly employed to evaluate not only the glycation level, but also the degree of oxidative stress. The percentages of glycated and glycooxidized species were calculated from the related MALDI spectra by the measurement of the related peak areas, without any other treatment of data. A linear relationship between HbA1c values and the total percentage of glycated and glyco-oxidized globins has been found, and its slope (< 1) has been rationalized by the uncorrected evaluation of glycated globins content in the standard samples employed for HbA1c measurements.

Chromatography, High Pressure Liquid↗

A study on lymphocyte subpopulation in diabetic mothers at delivery and in their newborn.

Despite the importance of immunological aspects in pregnancy, until now few studies have been reported on the cellular immune modifications of diabetic pregnancy and on the newborn of diabetic mothers. Therefore, we thought it of interest to evaluate cell immunity in diabetic pregnant women and in their newborn children. Fourteen pregnant women with Type 1 diabetes (T1DM), mean age (+/-SD) 30-4 yr, mean disease duration (+/-SD) 12+/-5 yr, 15 with gestational diabetes mellitus (GDM) (mean age 33+/-6 yr), and 21 healthy pregnant women (mean age 29+/-4 yr) were studied and their metabolic and immunological parameters were evaluated. Fifty newborn babies were examined for immunological evaluation. Mean fasting plasma glucose and HbA1c values were higher in T1DM and GDM patients than in controls. Total lymphocyte subsets were higher in T1DM and GDM patients, although there were no significant differences between the percentual values. In children of T1DM and GDM mothers absolute lymphocyte values were increased, whereas the natural killer (NK) subset had decreased values in both absolute and percentual terms. Our work shows that, with respect to healthy controls, both GDM and T1DM mothers have a significant increase in total lymphocytes, and newborns have a reduced number of NK lymphocytes. Lower numbers of NK lymphocytes are probably related to altered production of lymphokines during foetal life and may also represent a real immune deficit in monitoring against viral infections.

Adult↗

Erectile dysfunction in diabetic subjects in Italy. Gruppo Italiano Studio Deficit Erettile nei Diabetici.

OBJECTIVE: Our objective was to analyze the prevalence and risk factors for erectile dysfunction (ED) in men with diabetes in Italy in a cross-sectional study. RESEARCH DESIGN AND METHODS: Eligible for the study were men aged 20-69 years with a diagnosis of IDDM or NIDDM 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: Of the 9,868 diabetic men interviewed, 3,534 (35.8%) reported ED. The prevalence increased with age, from 4.6% in men aged 20-29 to 45.5% in those aged > or =60 years (test for trend, P = 0.0001). After taking into account the confounding role of age, men with NIDDM reported ED less frequently than did men with IDDM (odds ratio [OR], 0.7; 95% CI 0.6-0.8). In comparison with men reporting diabetes lasting < or =5 years, the ORs for ED were 1.3 and 2.0 for subjects with diabetes lasting 6-10 and 11-30 years, respectively. In comparison with men with good metabolic control, the ORs for ED were 1.7 and 2.3 in men with fair and poor control, respectively. A history of diabetes-related arterial, retinal, or renal diseases and neuropathy was associated with an increased risk of ED. Finally, in comparison with never-smokers, the ORs for ED were 1.5 (95% CI 1.3-1.6) for current smokers and 1.4 (95% CI 1.3-1.6) for ex-smokers. The OR increased with number of cigarettes smoked per day: in comparison with men smoking <12 cigarettes per day, the OR was 1.5 (95% CI 1.3-1.7) for those smoking > or =30 cigarettes day. CONCLUSIONS: The study offers a quantitative estimate of the prevalence of ED and of its main risk factors in Italian men with diabetes.

Adult↗

Rigiscan evaluation of specific nervous impairment in patients with diabetes and erectile disorders.

OBJECTIVE: A proposed new, minimally invasive, and painless method for studying impairment of the autonomic system of the penile region in type 2 diabetes patients. RESEARCH DESIGN AND METHODS: Thirteen subjects were selected from 150 patients with type 2 diabetes and erectile dysfunction who were studied in accordance with the National Institutes of Health consensus. The 13 subjects (group A), aged 55 +/- 8 years, had acceptable metabolic control (HbA1c, < 8%); no arterial or venous diseases or initial Peyronie's disease, as evaluated by penile Doppler ultrasonography and intracavernous prostaglandin E1 injection; and penile tumescence at the base (PTB) < 30 mm. Group B consisted of 13 control subjects with the same characteristics, including mean age (53.1 +/- 9 years), metabolic control (HbA1c, 7.3 +/- 0.7%), and duration of disease (8.3 +/- 0.7 years), but PTB was > 30 mm. Student's t test was used to evaluate differences in the results of autonomic cardiovascular tests, somatic tests (vibration perception threshold [VPT]), and diabetic neuropathy score (DNS) in both groups. The coefficient of variation of PTB was evaluated using the Rigiscan device (Dacomed, Minneapolis, MN), and Bayes' test was used to test sensitivity, specificity, and positive predictive values of the cardiovascular tests. RESULTS: Patients with PTB < 30 mm had significant (P < 0.05) impairment of parasympathetic tests (lying to standing, P < 0.02; standing to lying, P < 0.04; squat test, P < 0.03) compared with subjects with higher PTB values. No difference in DNS and VPT at the base and tip of the penis was found between the two groups. The variability of the test is 10% in normal subjects and 15% in both groups of patients. PTB sensitivity was 54%, specificity 89%, and positive predictive value 79%. CONCLUSIONS: In patients with diabetes and without vascular diseases, the PTB evaluated by Rigiscan is related to impairment of the autonomic nervous system. A PTB value < 30 mm may be considered a useful, noninvasive marker in studying parasympathetic damage of the penile region.

Alprostadil↗

Respiratory burst of neutrophils in diabetic patients with periodontal disease.

Periodontal disease, a frequent complication of diabetes mellitus, is the major cause of tooth loss. However, studies on neutrophil function in patients with this condition have yielded contradictory findings. The NADPH oxidase activity of 40 diabetic patients with periodontosis who were on metabolic control was evaluated and compared with that in 40 healthy subjects. Superoxide anion production was measured by a photometric method, with NBT reduction at 490 nm in a microplate reader and by a microscopic method, with a percentage of positive PMNs with granules of formazan in the cytoplasm. When the PMN respiratory burst was activated by phorbol myristate acetate (PMA), a protein kinase C (PKC) soluble activator, superoxide production of diabetics (4.31 +/- 1.67 A x 10(-3)/min) and normal subjects (4.25 +/- 1.25 A x 10(-3)/min) was comparable by photometric method, whereas a significantly defective response to opsonized zymosan was observed when the microscopic method was used (58 +/- 17% in diabetics and 66 +/- 18% in controls; p = 0.05). Therefore in patients with diabetes the impact on PMN function is of multifactorial origin, and is probably correlated to the glucose level and to glycation of PMN protein, such as NADPH oxidase or myeloperoxidase. Alternatively, glucose in PMN may be reduced by aldose reductase to polyols, and this pathway requires NADPH, the coenzyme for the respiratory burst. Moreover, we found that superoxide production in response to opsonized zymosan was reduced in diabetic patients. The activation of protein tyrosine kinase (PTK) is an important mechanism underlying transmembrane signaling and, moreover, protein tyrosine phosphorylations, stimulated by zymosan receptor-mediated activation, might be caused by the activation of specific PTK, whereas activation by PMA is probably mediated through another PKC type.

Chemotaxis, Leukocyte↗