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Biomedical subjects

F Fallucca

Publications and source records attributed to F Fallucca.

At least 19 recordsLinked to original sources

Two polyclonal antisera detect different AGE epitopes in human plasma samples.

Advanced glycation end products (AGEs), involved in the pathogenesis of diabetic complications, comprise a series of related chemical structures which might possess dissimilar immunogenic characteristics. In this study the levels of AGE in plasma samples from normal subjects (N=41) and diabetic patients (N=44) were measured by ELISA using two polyclonal antisera (named CF5 and CF199, respectively, and immunologically characterized) raised using two different immunogens and immunization techniques. Age levels were significantly higher in diabetic than in normal plasma samples (P<0.0001) with both antisera. However, CF199 detected higher AGE levels than CF5 both in normal (P<0.0001) and diabetic (P<0.005) samples. Pre-incubation with AGE-bovine serum albumin (BSA) caused the loss of most the reactivity of both antisera. Pre-incubation with carboxy-methyl-lysine-BSA (an oxidation-derived AGE) induced the loss of nearly all CF5 reactivity while CF199 retained a significant amount of activity against AGE antigens. Moreover, CF5 lost over 90% of its reactivity against BSA incubated with high glucose under non-oxidative conditions, suggesting its recognition of mainly oxidation-derived AGE epitopes. The different AGE levels measured by the two antisera suggests, therefore, that one single antiserum is unable to recognize all the various AGE epitopes which might be present, at any time, in tissues and body fluids in health and disease.

Diabetes Mellitus↗

Fetal pancreatic function in infants of diabetic and rhesus-isoimmunized women.

OBJECTIVE: To measure insulin and glucagon concentrations in amniotic fluid (AF) collected near term in basal conditions and after an arginine test in diabetic, rhesus-isoimmunized, and control pregnant women. METHODS: At baseline, AF was collected from 44 diabetic, 32 rhesus-isoimmunized, and 27 control pregnant women in late pregnancy. Fifty-two diabetic, six rhesus-isoimmunized, and nine control pregnant women had amniocentesis 2 hours after arginine infusion (30 g intravenous/30 minutes) at 33-36 weeks. RESULTS: Baseline AF glucose concentrations were significantly greater in diabetic women than the other conditions, and they related to the gestational age in the women with hemolytic disease of the newborn. Insulin and glucagon AF content of isoimmunized pregnancies overlapped controls, whereas insulin and insulin/glucagon molar ratios were significantly higher, and glucagon values lower, in diabetic pregnancies compared with isoimmunized and control pregnancies. In isoimmunized pregnancies, the AF concentrations of glucose, insulin, and glucagon were correlated with gestational age (less than 34, 34 weeks or more). The samples collected after arginine infusion, compared with those collected at baseline, showed significantly greater insulin and insulin/glucagon molar ratio values in diabetic (28 +/- 5 versus 11 +/- 1 microU/mL, P = .001; 29.4 +/- 1.7 versus 12.0 +/- 2.8, P = .001) and in Rh pregnant women (18 +/- 6 versus 7.7 +/- 0.7 microU/mL, P = .001; 30 +/- 9 versus 3.4 +/- 0.4 I/G, P = .001), whereas no significant difference was observed in the controls. CONCLUSION: Basal islet hormone concentrations in AF are modified by maternal diabetes and further influenced by arginine administration. Arginine produces an AF response that is similar in pregnancies complicated by diabetes mellitus and rhesus-isoimmunization, despite different (hyperglycemia and euglycemia) maternal blood glucose levels.

Adult↗

[The diabetic foot seen by the surgeon. Personal experience].

BACKGROUND: The aim of this study is to evaluate a major amputation risk criterion in diabetic patients with trophic lesions of the foot. The records of a series of 100 consecutive patients (65 males and 35 females) with diabetic foot ulcer treated in our surgical facilities between January 1992 and December 1997, in collaboration with diabetologists and podiatrists, have been reviewed retrospectively. METHODS: In 26 cases the ulcer involved both limbs and, therefore, the feet observed in this study have been 126. Accurate diagnosis of the underlying cause was the first step and in cases with a poor blood supply (69 limbs; 55%) unresponsive to medical therapy (44 limbs) vascular reconstruction (37 limbs), spinal cord stimulator (SCS) implantation (3 limbs) or major amputation (4 limbs) were performed. According to Wagner grading there were 42 grade 2 ulcers (33%), 38 grade 3 (30%), 43 grade 4 (34%) ad 3 grade 5 (3%). RESULTS: One patient died postoperatively after SCS implantation. All but 4 neuropathic ulcers (53 limbs) healed in a mean time (+/- SD) of 5.2 +/- 3.8 months and all but 10 vascular ulcers (59 limbs) healed in a mean time of 6.3 +/- 4.1 months. Of the latter group in 4 cases the patient died before ulcer healing while in 6 cases (8.7%) a major amputation was performed (in 2 cases after vascular reconstruction procedures). Minor amputations of the forefoot have been performed in 23 instances (33%) of vascular ulcer and in 10 cases (17%) of neuropathic ulcer. CONCLUSIONS: Since ischemia is the main risk factor for amputation, it is suggested that a particular effort should be made in improving the vascular diagnostic, both clinical and strumental, capabilities of our diabetologists and podiatrists in order to detect the vascular insufficiency in earlier stages.

Adult↗

[Diabetes and pregnancy: physio-pathogenetic and epidemiologic aspects].

Diabetes mellitus is one of the most common maternal illnesses resulting in congenital malformations. All complications of pregnancy, either with diabetes pregestational or gestational, are directly or indirectly related to the degree of metabolic control. If it is not treated properly, diabetes in pregnancy causes major problems for both mother and fetus. The only way to reduce complications to the minimum and locate them near to those of the normal population, is to achieve a good metabolic control. Multi-disciplinary approach in which obstetricians, physicians, paediatricians are involved, combined with intensive monitoring and therapy throughout pregnancy, could achieve successful results in women with complicated diabetes. This objective is subordinate to early diagnosis for gestational diabetes and planning of pregnancy for diabetic women.

Congenital Abnormalities↗

High frequency of polymorphism but no mutations found in the GLUT1 glucose transporter gene in NIDDM and familial obesity by SSCP analysis.

To evaluate whether a structural defect in the human glucose transporter gene GLUT1 could be involved in the aetiology of insulin resistance, a key factor of non-insulin-dependent diabetes mellitus (NIDDM) and obesity, we performed single-strand conformation polymorphism (SSCP) analysis in 40 subjects (20 NIDDM patients and 20 subjects with familial obesity). The GLUT1 gene, which is involved in basal glucose transport in most tissues, consists of ten exons and encodes a 492 amino acid protein. Population studies have shown a strong association between the X1 allele of an XbaI restriction fragment length polymorphism of the GLUT1 gene and NIDDM. We therefore performed SSCP analysis in NIDDM subjects known to carry at least one X1 allele. Variant SSCP patterns were detected in exons 2, 4, 5 and 9. Sequence analysis of the SSCP variants revealed the presence, in all exons examined, of silent mutations consisting of single-nucleotide substitutions with no amino acid changes. Both NIDDM and obese patients showed a high frequency of polymorphism in the sequence (50% and 35%, respectively). We conclude that the GLUT1 gene is unlikely to play a role in the aetiology of NIDDM and obesity. However, the strong association between the GLUT1 gene and NIDDM, together with the recent family studies showing linkage between chromosome 1p and NIDDM warrant further studies on this chromosomal region.

Adult↗

Glucose transporter (Glut1, Glut3) mRNA in human placenta of diabetic and non-diabetic pregnancies.

Transport of glucose into the cell is catalyzed by glucose transporters (Glut). Glut1 and Glut3 are expressed at various levels in many human tissues, including the placenta. It has been reported that ambient glucose can affect both glucose transport activity and expression of the Glut genes, and protein. To date, very few studies concerning Glut in the placenta have been published, and studies in vivo in human diabetic pregnancy are lacking. We therefore investigated placental Glut1 and Glut3 mRNA by Northern blot analysis in ten diabetic (five insulin dependent diabetes mellitus (IDDM), two non-insulin dependent diabetes mellitus (NIDDM) and three gestational diabetes mellitus (GDM)) and nine non-diabetic women. The quantitative results of specific mRNA/beta-actin ratios were expressed as arbitrary units. The results were evaluated according to metabolic and clinical findings. Glut1 and Glut3 mRNA values in diabetic and non-diabetic pregnant women were similar. The metabolic environment seems to affect the Glut3 mRNA levels in IDDM pregnant women but not the control women. In addition, Glut3 mRNA decreased in late pregnancy in the diabetic but not in the control women. Moreover, Glut1 mRNA levels were correlated with maternal age in the diabetic as well as in the control women (significantly). Finally, an inverse correlation was found between Glut1 mRNA levels and placental weight (in both diabetic and non-diabetic women). These results, although preliminary, shed some light on the function of these glucose transporters in normal as well as in diabetic pregnancies and prompt us to carry out a further investigation to better elucidate fetomaternal metabolic correlation at the placental level.

Adult↗

Blood pressure monitoring in diabetic pregnancy.

Hypertensive disorders which complicate 5-10% of all pregnancies are more frequent in diabetic women. We longitudinally monitored blood pressure (BP) for a 24 h period in 54 diabetic out patients, at each trimester of pregnancy, in order to observe the relationship between the blood pressure behaviour and the main clinical features of these subjects. A relationship was found between blood pressure and the diabetes type. In insulin-dependent diabetes mellitus (IDDM) women, the age of diagnosis and the diabetes duration played the major role whereas, in non insulin-dependent diabetes mellitus (NIDDM) women only the patients' age was correlated with the BP levels. Higher BP levels were found in women belonging to the White class D, and whose diabetes duration was more than 10 years. An interesting correlation was also demonstrated between BP and insulin requirement, in late pregnancy as well as the time of delivery. Early in pregnancy, BP levels, even if within normal range, were undoubtedly higher in those women who developed hypertension compared to those who continued to be normotensive. Daytime BP values were always found higher than night-time BP values but, the physiological biorhythm seemed to be altered at the end of pregnancy.

Adolescent↗

Diabetes and pregnancy: prophylaxis of genital infections.

Diabetic pregnant women have many potential reasons to have genital infections such as poor metabolic control and impairement of leucocyte function. Relative immune deficiency exists in pregnancy. This study was designed to test the hypotheses that pregnant patients with insulin-dependent diabetes have a higher rate of ante partum genital infections when compared with a pair-matched control population. Two groups of pregnant women consisting of 23 patients with and 23 without diabetes mellitus, underwent colposcopy and cytology between 16th and 24th week of gestation to detect the presence of human papilloma virus (HPV), Gardnerella vaginalis, Candida albicans and aspecific infections. No significant differences were observed between the two groups.

Adult↗

Telemedicine in the treatment of diabetic pregnancy.

Good diabetic control requires that treatment be continuously adapted to the patient behavior. We investigated whether the use of telemedicine could present an advantage to the management of the diabetic woman during pregnancy. A system completely automatic (DIANET system) was used. Twenty IDDM women participated in the study: 10 treated by telemedicine and 10 by conventional system, at times "entry" (9.5 weeks), "basal" (9.5-16.8 weeks), "1st month" of investigation, and "end" (near delivery). All women used intensified protocols of insulin administration. The treatment with DIANET vs conventional showed a better metabolic control as estimated by profile of blood glucose absolute values (at time "end": values significantly lower before breakfast: 87 +/- 6 vs 104 +/- 4 mg, lunch: 85 +/- 5 vs 104 +/- 4 mg, and after dinner: 102 +/- 5 vs 124 +/- 6 mg). These results were associated with higher insulin doses in the DIANET vs conventional treatment, and a significant reduction of hypoglycemic reaction in both group. Our results suggest that telemedicine-DIANET is a practical way of providing specialist care in the pregnancy area.

Adult↗

Pathophysiology of diabetes in pregnancy.

Pregnancy is attended by extensive hormonal readjustments on the part of the mother. Almost every endocrine tissue participates in adaptive changes that maintain the metabolic state of the woman during normal pregnancy. Endocrinologic and metabolic adaptations characterizing pregnancy in women with normal carbohydrate metabolism also impinge upon the metabolism of the diabetic during pregnancy. In the diabetic woman the impairment of metabolism which follows the modifications of endocrinologic adaptations induces a compromised metabolic "milieu" in both the foetal blood and amniotic fluid in which swallows the fetus, promoting several damages according to the gestational age in the conceptus. Disturbances of intermediary metabolism undoubtedly play a major role in the etiology of complications of diabetic pregnancy. However an increasing amount of evidence is accumulating that suggests that abnormalities of immune function may also be operative in both the mother and fetus as well as in placenta. Finally there is limited information on the long-term prognosis of infants born to mothers with pre-gestational and gestational diabetes mellitus. Follow-up studies have mainly focused on two aspects: the risk of appearance of diabetes later in life, and psychosomatic development. Genetic aspects and the role of metabolic disorders during pregnancy must be once again emphasized.

Adult↗

Glucose transporters (GLUT 1, GLUT 3) mRNA in human placenta of diabetic and non-diabetic pregnancies.

Glucose transporters (GLUT) catalyse the transport of glucose in many human tissues, including the placenta. On the other hand glucose concentrations can affect both glucose transport activity and level of GLUT mRNA and protein. Up to now very few studies, concerning GLUT in the placenta appeared and studies in vivo in human diabetic pregnancy are lacking. Therefore we investigated placental GLUT 1 and GLUT 3 mRNA in 10 diabetic (5 IDDM, 2 NIDDM, 3 GDM) and 9 non-diabetic women. GLUT 1 mRNA was found significantly correlated with maternal age (> 30 vs < 30 years: p < 0.025), with placental weight (> 575 vs < 575 g: p < 0.05), while GLUT 3 mRNA decreased significantly in late gestation of diabetic women (38-40 vs < 38 weeks: p < 0.025). In addition GLUT 3 was significantly lower in the diabetic than in non-diabetic women in late gestation. These preliminary results deserve to better elucidate feto-maternal carbohydrate metabolism at the placental level in normal as well as diabetic pregnancy.

Adult↗

Levels of advanced glycosylation end-products (AGE) in sera of pregnant diabetic women: comparison between type 1, type 2 and gestational diabetes mellitus.

The chronic hyperglycemia can lead to an increase of the advanced glycosylation end-products (AGE) levels on proteins and macromolecules. Abnormal levels of AGE in several tissues has been associated with the pathogenesis of late diabetic complications. In diabetic pregnant women, high AGE levels might influence the delicate maternal-fetal balance and therefore alter the pregnancy outcome. In this preliminary study, we have measured the AGE in sera of 44 diabetic women in two trimester. Sixteen sera from non diabetic pregnant women have been used as controls. The AGE have been analyzed by means of an ELISA method with an antiserum anti-RNAse-AGE, produced in the Laboratory of Clinical Biochemistry of the Istituto Superiore di Sanità. Diabetic patients type 1 and type 2, in good metabolic control, showed normal AGE levels at both trimester. Patients with gestational diabetes showed significantly high serum AGE levels (p < 0.05). A more extended study will give better insight on the association between AGE levels and a physiopathology of diabetic pregnancy.

Adult↗

IGF-1 levels in diabetic pregnant women and their infants.

Plasma IGF-1 was measured in 38 diabetic pregnant women (DPW) and in 12 non diabetic pregnant women (NDPW) during the 1st, 2nd and 3rd trimester of pregnancy. IGF-1 was measured in the cord blood of 24 infants of diabetic mothers (IDDM) and IGF-1 in 11 infants of non diabetic mothers (NIDDM). A progressive and significant (p < 0.0001) increase of IGF-1 values was found throughout the pregnancy both in DPW and NDPW IGF-1 (149 +/- 18 ng/ml vs 181 +/- 14 ng/ml, 184 +/- 17 ng/ml vs 232 +/- 25 ng/ml, 279 +/- 20 ng/ml vs 325 +/- 17 ng/ml). Furthermore IGF-1 decreased significantly soon after delivery in both groups of women. In type 1 diabetic pregnant women IGF-1 values were significantly lower than the controlled non diabetic patients. IGF-1 in the cord blood was significantly higher in IDDM than in NIDDM 86 +/- 7 ng/ml and 62 +/- 7 ng/ml respectively (p < 0.03). In addition, DPW plasma levels IGF-1 were positively correlated with the weight of the placenta (r = 0.233, p < 0.03) and negatively correlated with the diabetes duration (r = 0.412, p < 0.05). No correlations were found between IGF-1 cord blood concentrations and gestational age, birth weight and length, but there was a significant correlation with weight percentile (r = 0.846, p < 0.001). No correlation was found between maternal IGF-1 plasma levels and other parameters like insulin need, weight gain, metabolic control and time of delivery.

Adult↗

Autoimmune markers of diabetes in diabetic pregnancy.

Gestational diabetes mellitus (GDM) has been described in 1-3% of pregnancies and increases the risk (up to 60-70%) to subsequently developing an overt diabetes (generally of type 2 non insulin-dependent diabetes mellitus (NIDDM)). Several humoral autoimmune phenomena have been described in GDM: islet cell antibodies (ICA) have been found and it was shown that ICA+ patients tend to have a worse glucose tolerance. Recently, autoantibodies against glutamic acid decarboxylase (GAD), were detected in type 1 diabetic sera before or at the onset of the disease; these markers, as well as ICA and insulin antibodies, seem to have a predictive value for the onset of the disease. Aim of our study was to investigate the presence of GAD65 in 83 GDM, 79 NIDDM and 64 pregnant normal women in late gestation. GAD Ab positivity was found (0.035 index as limit) only in GDM and NIDDM (3.6% in GDM, 3.8% in NIDDM, and nothing in control women). These results indicate that GAD positivity in GDM overlaps that of NIDDM, suggesting that the two diabetic populations have the same predisposition to develop a type 1 diabetes mellitus, and likely they share the same disease. Further studies need to clarify whether this prevalence of GAD positivity may unmask type 1 diabetes in both GDM and NIDDM diabetic women.

Adult↗

Plasma met-enkephalin levels in diabetic patients: influence of autonomic neuropathy.

The presence of opioid peptides within pancreatic islets in several animal species and in humans suggests that these peptides could play a role in pancreatic endocrine secretion, influencing glucose metabolism. We measured plasma met-enkephalin (met-Enk) levels in eight neuropathic (four with insulin-dependent diabetes mellitus [IDDM] and four with non-insulin-dependent diabetes mellitus [NIDDM]) and eight nonneuropathic (four IDDM and four NIDDM) diabetic patients to study met-Enk secretion in diabetic patients with asymptomatic autonomic neuropathy. Plasma met-Enk levels were significantly lower in neuropathic compared with nonneuropathic patients both in the IDDM group (28.7 +/- 4.8 v 61.6 +/- 4.1 pg/mL, P < .0025) and in the NIDDM group (26.5 +/- 3.6 v 44.3 +/- 4.6 pg/mL, P < .0125). This study suggests that the presence of neuropathy in diabetic patients, even if asymptomatic, is associated with a significant decrease of plasma met-Enk levels, thus contributing to a worsening of metabolic control under stress conditions.

Adult↗

Combined therapy with insulin and sulfonylurea for the treatment of new-onset insulin-dependent diabetes mellitus.

The progressive B-cell destruction at the onset of type 1 diabetes and the relevance of residual B-cell function to metabolic control prompted us to try to prevent further B-cell destruction in new-onset type 1 diabetic patients. Having already shown positive effects of sulfonylreas in long-standing IDDM patients, we decided to try the association of gliclazide with insulin in newly diagnosed IDDM patients. Therefore, 22 patients were randomly assigned to either gliclazide, 160 mg/24 h, or placebo (in association with standard insulin treatment) from the third week since the onset of the disease. Patients were studied every 6 months for 18 months. The insulin need was similar in the two groups at time 0, but thereafter it steadily decreased in the GCZ group becoming at 6, 12 and 18 months, respectively 65%, 42% and 39% of that of the PL group. The metabolic control was very similar in the two groups throughout the study. The residual B-cell function (fasting and post-breakfast C peptide), which was similar in the two groups at time 0, remained unchanged or improved in the GCZ group, whereas it decreased in the PL group. In conclusion, the combined insulin-gliclazide treatment appeared to improve B-cell function during the first 18 months of type 1 diabetes, inducing a major reduction of the insulin need with respect to patients treated with insulin alone.

Adolescent↗

Amniotic fluid insulin and C peptide levels in diabetic and nondiabetic women during early pregnancy.

Thanks to the widespread use of amniocentesis, glucose, insulin, and C peptide have often been measured in amniotic fluid (AF) during late gestation, but little is known about their concentrations during early pregnancy. To better understand early fetal beta-cell function under normal conditions and in the presence of maternal diabetes, we measured glucose, insulin, and C peptide in the AF collected during weeks 15-22 in 77 healthy and 9 diabetic women undergoing amniocentesis for clinical indications and compared the results with those obtained during late pregnancy (weeks 34-36). The AF C peptide concentration was higher in diabetic women (102 +/- 53 vs. 38 +/- 2 pmol/L), in the women with a family history of diabetes (41 +/- 6 vs. 35 +/- 2 pmol/L), after the 19th week of gestation (46 +/- 5 vs. 35 +/- 2 pmol/L; in the presence of lower glucose concentrations), and in the presence of maternal plasma glucose levels greater than 5.56 mmol/L (42 +/- 3.5 vs. 34 +/- 2 pmol/L). The comparison between early and late gestation showed decreasing glucose and increasing C peptide concentrations in both healthy and diabetic women (in the latter, C peptide values were always 3 times higher), whereas the insulin concentration was increased in late gestation only in diabetic women. The AF C peptide/insulin molar ratio increased throughout pregnancy in both healthy (from 0.97 +/- 0.06 to 4.3 +/- 1.2) and diabetic (from 2.9 +/- 1.1 to 13.2 +/- 1.6) women. These parallel changes suggest that the fetal clearance and/or degradation of insulin and C peptide may greatly change during both normal and diabetic gestation.

Adult↗

Sorbitol malabsorption and nonspecific abdominal symptoms in type II diabetes.

Some data suggest that sorbitol intake may be responsible for diarrhea in diabetic patients. One hundred thirteen hydrogen breath tests were performed in type II diabetics (72) and normal controls (41) after oral loads of sorbitol ranging from 2.5 to 20 g in iso-osmolar solutions to assess the role of malabsorption of this compound in the genesis of abdominal symptoms. The prevalence of sorbitol malabsorption and abdominal symptoms, peak (Cmax H2) and total (Ctot H2) hydrogen production, and mouth to cecum transit time (MCTT) did not differ in type II diabetics and controls. Malabsorption was observed more frequently with the highest doses of sorbitol (10% of patients at a dose of 2.5 g and approximately 75% at 20 g). Symptoms, usually consisting of mild discomfort and abdominal distension, were observed only after sorbitol loads of 10 and 20 g in 27.2% of the diabetics and in 36.3% of the controls. Diarrhea was present in three subjects (two diabetics and one control) only at a dose of 20 g. These data indicate that it is highly unlikely for sorbitol to play a role in inducing diabetes diarrhea. A moderate (up to 10 g) sorbitol intake is not contraindicated in type II diabetics.

Abdomen↗