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R Bonfanti

Publications and source records attributed to R Bonfanti.

At least 19 recordsLinked to original sources
PubMed1998

Parameters associated with residual insulin secretion during the first year of disease in children and adolescents with Type 1 diabetes mellitus.

Factors associated with residual insulin secretion and spontaneous remission in Type 1 diabetic patients are important in the evaluation of treatment aimed at modifying the natural history of Type 1 DM. We investigated the effect of parameters at onset on residual beta cell function in 215 Type 1 DM children and adolescents. Blood gas analysis, HLA, GAD and IA-2 antibodies before the start of insulin treatment were recorded for each patient. Residual C-peptide secretion was assessed by the glucagon test, and parameters of metabolic control (HbA1c and insulin dose U kg(-1) day(-1)) were examined at disease onset and after 3, 6, and 12 months. Residual C-peptide secretion throughout the first year of disease was significantly reduced in patients with disease onset before age 5. Multiple regression analysis showed that low pH at onset showed a significant and independent association with reduced C-peptide at 3 months (p = 0.02) and that the detection of GAD antibodies had a significant independent association with decreased C-peptide secretion at 6 months of follow-up (p = 0.02). Insulin requirement was higher in the youngest patients group and in patients with GAD antibodies. Spontaneous insulin remission (HbA1c <6% and insulin <0.3 U kg(-1) day(-1)) occurred in 22/192 (11%) patients at 3 months of follow-up, in 15/190 (8%) patients at 6 months and in 8/169 (5%) patient at 12 months. Remission was more prevalent in older patients (p = 0.01) and in patients without detectable GAD antibodies: (14/64 vs 8/128, p = 0.001). Sex, IA-2 antibodies and HLA DR were not independently associated with C-peptide secretion, insulin requirement or remission in the first year of Type 1 DM. This study confirms the association of young age, severe acidosis at disease onset, and GAD antibodies with decreased residual beta-cell function and spontaneous remission during the first year of insulin treatment. These factors should be considered in trials evaluating therapies to retain beta-cell function and induce remission at and after disease onset.

Adolescent↗
PubMed1998

Residual beta-cell function and spontaneous clinical remission in type 1 diabetes mellitus: the role of puberty.

To investigate the role of puberty on spontaneous clinical remission and on secretion of residual C-peptide during the first year of type 1 diabetes mellitus, we studied 77 pre-pubertal, 39 pubertal and 41 post-pubertal type 1 diabetic patients. Spontaneous partial clinical remission (HbA1c within the normal range and insulin dose less than 0.3 U x kg(-1) body weight x day(-1) lasting for at least 10 days) decreased with duration of diabetes: months 3 vs 6 vs 12, respectively 13 vs 7 vs 4% (P<0.025). Remission was higher in post-pubertal than pubertal and prepubertal patients: month 6 respectively 20 vs 5 vs 1% (P<0.001). Secretion of C-peptide was significantly lower in pre-pubertal than the other two groups of patients. Basal and stimulated C-peptide secretion were higher in patients in clinical remission than in those who were not: basal value 0.4 (0.26-0.53) vs 0.28 (0.14-0.4) nmol/l (P<0.05); stimulated value 0.63 (0.5-0.95) vs 0.56 (0.31-0.74) nmol/l (P<0.05). Spontaneous remission is less frequent in children and adolescent patients than in adult post-pubertal patients, but different mechanisms may be involved. Low residual insulin secretion seems implicated in children meanwhile low insulin sensitivity could be more important in pubertal patients.

Adolescent↗
PubMed1998

Growth changes in children and adolescents with short-term diabetes.

OBJECTIVE: Height and weight changes during the first 3 years of diabetes were prospectively followed in 152 diabetic children and adolescents. RESEARCH DESIGN AND METHODS: The study sample consisted of 152 Caucasian diabetic patients (84 boys; 68 girls) followed from diabetes onset in the Paediatric Diabetes Unit and 80 Caucasian normal subjects (49 boys; 31 girls) assessed in the Outpatient General Paediatric Clinic of the same hospital for routine examination and not affected by problems that might influence growth. Diabetic patients and control subjects were consecutively enrolled in the study between 1989 and 1992; diabetic patients with positive markers for celiac disease (positive antiendomysial antibodies) and thyroid disease (positive antimicrosomial antibodies) or any other chronic disease were not considered in the study. Mean age of diabetic patients (8.9 +/- 4.1 years) and control subjects (8.5 +/- 4.2 years) at recruitment in the study was similar. RESULTS: At onset of diabetes, the mean height expressed as the height standard deviation score (HSDS) was significantly greater than the expected values (P < 0.0001) and was independent of sex and pubertal stage. During the first 3 years of diabetes, HSDS decreased significantly (F = 6.9; P < 0.001). Meanwhile, growth velocity as standard deviation score (SDS) decreased significantly between the 1st and 2nd year (-0.12 +/- 2.1; -0.76 +/- 2.6, respectively; P < 0.05), but it was similar between the 2nd and 3rd year of diabetes. Weight expressed as SDS increased significantly during the first 2 years of diabetes but not thereafter. Height changes during the study period were independent from pubertal stage and sex. Metabolic control and insulin requirement, in our series, were not clearly related to height and weight changes. CONCLUSIONS: Diabetic patients at onset of diabetes are taller than age- and sex-matched nondiabetic subjects. During the first years of the disease, linear growth decreases independently of metabolic control and weight changes.

Adolescent↗
PubMed1998

Two-step islet autoantibody screening for risk assessment of type 1 diabetes in relatives.

OBJECTIVE: To examine the performance of islet cell antibodies (ICAs) and antibodies to glutamate decarboxylase (GADA), IA-2 (IA-2 antibody [IA-2A]), and insulin (insulin autoantibody [IAA]), alone and in combination, in assessing type 1 diabetes risk within type 1 diabetic families to identify a practical and effective screening strategy for predicting type 1 diabetes in relatives. RESEARCH DESIGN AND METHODS: ICA, GADA, IA-2A, and IAA were determined in 806 first-degree relatives participating in a prospective type 1 diabetes family study (median follow-up 6.17 years, range 0.6-8.3). The conferred risk of developing type 1 diabetes within 6 years was evaluated by Kaplan-Meier for each antibody marker, used alone or in combination. RESULTS: ICAs were detected in 3%, GADA in 5.1%, IA-2A in 2.5%, and IAA in 3.7% of relatives; > or =1 antibody markers were detected in 10.7% of relatives and > or =2 were detected in 1.9% of relatives. The risk of type 1 diabetes at 6 years was 1.5% in relatives with only 1 marker and 24.8% in relatives with > or =2 markers. As a practical and effective strategy for type 1 diabetes risk assessment in relatives, this study indicates a first-step screening based on GADA and IA-2A measurement--which identified 6.5% of relatives, including all who developed the disease, with a 6-year type 1 diabetes risk of 9.0%--followed by a second step based on ICA and IAA measurement in relatives with either GADA or IA-2A, which identified a total of 1.9% of all relatives as having > or =2 markers, and a 6-year risk of 24.8%, including 6 of 7 who developed type 1 diabetes. CONCLUSIONS: A two-step antibody screening, based first on GADA and IA-2A and then on ICA and IAA measurements in identified individuals, is likely to be a practical, sensitive, and effective strategy for predicting type 1 diabetes in first-degree relatives.

Adult↗
PubMed1997

Bone modeling indexes at onset and during the first year of follow-Up in insulin-dependent diabetic children.

Osteopenia has been described as a complication of insulin-dependent diabetes mellitus (IDDM). We measured bone modeling indexes during the first year of IDDM. At each time point the values obtained from diabetic children have been compared with those of control subjects. We selected 27 prepubertal children with IDDM (6.35 +/- 2.16 years). We also enrolled 30 healthy prepubertal children of comparable age (5.85 +/- 3.05 years). Height, height standard deviation scores, glycated haemoglobin (HbA1C), basal c-peptide concentrations, insulin dose, serum concentrations of procollagen type I C-terminal propeptide (PICP), and collagen type I C-terminal telopeptide (ICTP) were measured at onset of IDDM and at 3, 6 and 12 months. ICTP was in the normal range at onset of IDDM and decreased during the follow-up to reach a significant difference compared to controls after 3, 6 and 12 months of insulin treatment (P < 0.04). PICP concentrations increased significantly at 3 months (P = 0.05) compared to onset. At 3 and 12 months PICP values were significantly higher than those of control children (P = 0.04). Correlations were found between PICP concentrations and HbA1C and c-peptide at onset of diabetes (r = -0.45 and r = 0.47, respectively). Bone formation at onset of IDDM is not impaired; the introduction of insulin therapy, together with the achievement of a good metabolic control, determines an increase of bone matrix formation coupled with a decrease of bone resorption, that determines a positive balance of bone modeling.

Adolescent↗
PubMed1997

Frequency and correlates of severe hypoglycaemia in children and adolescents with diabetes mellitus.

UNLABELLED: Frequency and correlates of severe hypoglycaemia have been retrospectively analysed in a cohort of diabetic children and adolescents with median (range) age 14.5 (3.2-25.5) years followed from the onset of the disease by the same diabetic clinic. During the years 1992-1994, 53 of the 187 patients reported 74 hypoglycaemic episodes: the average frequency of hypoglycaemia during the 3 years surveyed was 14.9 episodes/ 100 patients per year. Frequency of hypoglycaemia decreased significantly with age (chi 2 = 24.1; P < 0.0001) and was independent of duration of diabetes. Glycosylated haemoglobin and insulin dose were similar in patients with and without hypoglycaemia, matched for age and duration of diabetes. One out of two hypoglycaemic episodes occurred during sleep and no explanation was available for 50% of episodes. CONCLUSION: In this study severe hypoglycaemia was more frequent in young children than in adolescents and was independent of metabolic control and insulin dose.

Adolescent↗
PubMed1996

Association of IA-2 autoantibodies with HLA DR4 phenotypes in IDDM.

Insulin, glutamate decarboxylase (GAD) and the protein tyrosine phosphatase-like molecule IA-2 are major targets of humoral autoimmunity in insulin-dependent diabetes mellitus (IDDM). These autoantibodies are heterogeneous with respect to age and patient human leukocyte antigen (HLA) phenotype. We have previously demonstrated that GAD and IA-2 antibodies potentially identify different subsets of IDDM patients. The aim of this study was to determine whether GAD and IA-2 autoantibodies were associated with different HLA DR phenotypes. We studied 160 patients with IDDM onset before age 16 years. At disease onset serum was tested for GAD and IA-2 antibodies by immunoprecipitation by in vitro-translated 35S-methionine labelled recombinant proteins. IA-2 antibodies were significantly associated with HLA DR4: 67 (86%) of 78 patients with HLA DR4 vs 31 (38%) of 82 non-DR4 patients had IA-2 antibodies (Pc < 0.0001) and IA-2 antibody levels were higher in patients with HLA DR4 (Pc < 0.0001). In contrast, GAD antibodies were more prevalent (Pc < 0.05) and antibody levels highest (Pc < 0.01) in patients with HLA DR3 phenotypes. These data provide further evidence that, in IDDM, production and titre of major autoantibody specificities are associated with HLA class II alleles.

Alleles↗
PubMed1995

[Predictive value of ultrasonography in the study of aortic abdominal aneurysms].

Several authors have collected a great deal of data in the study of abdominal aorta aneurysm through the swift diffusion of ultrasonography in the abdominal diagnostics. The authors illustrate their experience confirming the excellent reliability of ultrasonography in the diagnosis of abdominal aorta aneurysms with respect to other methods of imaging (Angiography, CAT, etc) not with a view to replacing them but as a useful means of screening.

Aortic Aneurysm, Abdominal↗
PubMed1995

[Unusual case of reappearing biliary ileus in a cholecystectomized patient with late stenosis of ileo-ileal anastomosis].

An unusual case of alternating jejunal obstruction, caused by a former latero-lateral anastomosis stenosis, complicated by two stones into the afferent jejunal tract bottom, is described. The anamnestic data of previous cholecystectomy and operative finding of no one biliary fistula clue, make the authors doubtful about a hypothetic calculi migration: it is likely calculi are formed into the bowel.

Anastomosis, Surgical↗
PubMed1994

Disseminated intravascular coagulation and severe peripheral neuropathy complicating ketoacidosis in a newly diagnosed diabetic child.

Disseminated intravascular coagulation is a very rare complication of diabetic ketoacidosis. Central nervous system palsy but not peripheral neuropathy has been reported in these patients. On the other hand, signs of peripheral neuropathy may also be present at the onset of diabetes, but they are usually reversible within a few days after correction of the metabolic derangement. We describe an unusual case of mononeuritis multiplex syndrome still present after 2 months of follow-up in a child with diabetic ketoacidosis complicated by disseminated intravascular coagulation at the onset of insulin-dependent diabetes. These neurological impairments may be consistent with functional neural lesions due to vasa nervorum thrombosis and prolonged ischaemia.

Blood Pressure↗
PubMed1994

Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives.

Prediction of insulin-dependent diabetes mellitus (IDDM) is still largely based on islet cell antibodies (ICAs), but it may be improved by combined analysis with other humoral markers. We examined autoantibodies to insulin (IAAs), glutamic acid decarboxylase (GAD), and M(r) 37,000 and M(r) 40,000 fragments of islet antigens (37 and 40 kDa) together with ICA subtypes in 101 family members with ICAs > or = 10 Juvenile Diabetes Foundation units (JDF U) followed for up to 14 years, of whom 18 have developed IDDM. Life-table analysis showed a 43% risk of IDDM within 10 years for those with ICAs > or = 10 JDF U, rising to 53% for those with ICAs > or = 20 JDF U. The risk for ICAs > or = 10 JDF U was 62% in the family members in the youngest age quartile (< 13.2 years) and fell with increasing age to 4% in those > 40.7 years of age (P = 0.03). ICAs > or = 10 JDF U combined with IAAs gave a risk of 84% (P = 0.03 compared with IAA-), and ICAs > or = 10 JDF U combined with GAD antibodies gave a risk of 61% (P = 0.018). The risk for ICAs > or = 10 JDF U with antibodies to 37-kDa antigen was 76% (P < 0.0001). Risk increased with the number of autoantibodies, from 8% for ICAs alone to 88% with > or = 3 autoantibodies (14 cases detected) (P < 0.0001). The increased risk associated with multiple antibodies was observed independent of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Nicotinamide and insulin secretion in normal subjects.

Nicotinamide has been given both before and after clinical onset of Type 1 (insulin-dependent) diabetes mellitus in an attempt to prolong beta-cell survival. Nicotinic acid, structurally similar to nicotinamide, induces insulin resistance and increases insulin secretion in healthy individuals. It is not known if nicotinamide has similar effects. Since insulin secretion, as measured by the acute insulin response to intravenous glucose, is used to predict diabetes and to monitor therapy, the effects of nicotinamide must be established before trials in individuals at high risk of progression to Type 1 diabetes can be interpreted. Intravenous tolerance tests were performed according to the ICARUS standard protocol in 10 healthy, adult subjects (age 32 +/- 5.7 years) before and after 14 days of treatment with nicotinamide 25 mg.kg-1.day-1. The acute insulin response after nicotinamide did not differ from the control study, whether measured as the incremental 0-10 min insulin area (278 +/- 142 vs 298 +/- 130 mU.l-1.10 min-1) or as the 1 +/- 3 min insulin level (78 +/- 39 vs 81 +/- 44 mU/l). The late insulin response was equally unaffected, as were basal insulin (5.2 +/- 1.6 vs 5.6 +/- 2.1 mU/l) and glucose (5.0 +/- 0.4 vs 4.9 +/- 0.2 mmol/l) levels and glucose disposal rates (1.98 +/- 0.88 vs 2.04 +/- 0.68%/min). Nicotinamide does not affect insulin secretion and glucose kinetics in normal subjects, confirming its suitability for trials designed to delay or prevent the onset of Type 1 diabetes.

Adult↗
PubMed1993

Decrease of glomerular hyperfiltration in short-term diabetic adolescents without microalbuminuria.

OBJECTIVE: This study has been designed to follow prospectively the GFR and UAE of young patients with short-term IDDM and normal UAE. RESEARCH DESIGN AND METHODS: The study population consisted of 19 patients with glomerular hyperfiltration and 19 patients with normal GFR, matched for duration of diabetes and age. GFR has been assessed by radioisotopic tracer and UAE by RIA at the beginning of the study and after 30.5 +/- 10.4 mo of follow-up. RESULTS: GFR decreased in the two groups btt delta GFR of patients with glomerular hyperfiltration was greater than delta GFR of patients with normal GFR (0.83 +/- 0.55 vs. 0.28 +/- 0.63 ml.min-1.mo-1; P < 0.01). UAE, BP, and prevalence of microalbuminuria were comparable between the two groups at follow-up. Rate of fall of GFR was positively correlated with initial GFR (r = 0.59, P < 0.001) but not with initial UAE, BP, or changes in HbA1C, UAE, BP, or pubertal development during follow-up. CONCLUSIONS: Investigation of kidney function in children and adolescents with IDDM over a 3-yr follow-up period shows that glomerular hyperfiltration is characterized by a greater decline in GFR without an increased rate of appearance of microalbuminuria, than in patients with normal GFR.

Adolescent↗
PubMed1991

Induction of specific storage organelles by von Willebrand factor propolypeptide.

Endothelial cells store the multimeric adhesive glycoprotein von Willebrand factor (vWf), which promotes the formation of a platelet plug at the site of vessel injury. To investigate the packaging of vWf into the granules called Weibel-Palade bodies, we expressed pro-vWf cDNA and cDNA lacking the prosequence in a variety of cell lines. Storage granules formed only in cells that contain a regulated pathway of secretion. Furthermore, packaging required the prosequence. Pro-vWf, lacking the C-terminal region involved in interchain disulfide bonding, formed granules. We conclude that the signal for storage is universal in that an adhesive glycoprotein can be stored by a hormone-secreting cell; the storage of vWf is independent of its covalent multimeric structure; the unusual rod shape of Weibel-Palade bodies is due to vWf; and the vWf propolypeptide is necessary for the formation of vWf storage granules.

Animals↗
PubMed1991

von Willebrand factor and the endothelium.

Endothelial cells are the principal source of plasma and basement membrane von Willebrand factor (vWF). To arrive at its biologically active multimeric form, vWF undergoes a series of intracellular processing steps. The protein is synthesized as a large precursor pro-vWF, which dimerizes in the endoplasmic reticulum through disulfide bonds located in the carboxyl-terminal portion of the subunit. Only dimers are transported to the Golgi apparatus. Expression of truncated pro-vWF subunits, which lack the last 20 kd, abolishes the requirement for dimerization and thereby allows the monomeric protein to be secreted. Another requirement for intracellular transport from the endoplasmic reticulum is N-linked glycosylation. Inhibition of N-linked glycosylation prevents exit of both the wild-type and the truncated vWF from the endoplasmic reticulum. In the acidic environment of the trans-Golgi and post-Golgi compartments, pro-vWF dimers multimerize by a second set of interchain disulfide bonds. The presence of the vWF propolypeptide and acidic pH conditions are necessary for the multimerization process. The largest vWF multimers are stored in endothelial cell-specific organelles called Weibel-Palade bodies. At the site of vascular injury and inflammation, physiologic secretagogues such as thrombin, fibrin, and histamine may cause release of these large, biologically potent vWF multimers from the Weibel-Palade bodies into the surrounding blood and subendothelium.

Endoplasmic Reticulum↗
PubMed1991

Simultaneous determination of retinol, tocopherols, carotenes and lycopene in plasma by means of high-performance liquid chromatography on reversed phase.

The determination of the vitamins A and E as well as of carotenes and lycopene is important for studies of cardiovascular diseases and cancer. A method for laboratory routine is reported to separate simultaneously retinol, tocopherols, alpha- and beta-carotene, lycopene and beta-cryptoxanthin in human plasma or serum by HPLC on reversed phase starting from one extract. Two detectors with programmable wavelength are used sequentially, a spectrophotometer for the detection of the carotenoids in the visible region and a fluorometer for the assay of retinol and the tocopherols.

Carotenoids↗