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R Buzzetti

Publications and source records attributed to R Buzzetti.

At least 37 records · Page 2Linked to original sources
PubMed1998

Fine mapping of the diabetes-susceptibility locus, IDDM4, on chromosome 11q13.

Genomewide linkage studies of type 1 diabetes (or insulin-dependent diabetes mellitus [IDDM]) indicate that several unlinked susceptibility loci can explain the clustering of the disease in families. One such locus has been mapped to chromosome 11q13 (IDDM4). In the present report we have analyzed 707 affected sib pairs, obtaining a peak multipoint maximum LOD score (MLS) of 2.7 (lambda(s)=1.09) with linkage (MLS>=0.7) extending over a 15-cM region. The problem is, therefore, to fine map the locus to permit structural analysis of positional candidate genes. In a two-stage approach, we first scanned the 15-cM linked region for increased or decreased transmission, from heterozygous parents to affected siblings in 340 families, of the three most common alleles of each of 12 microsatellite loci. One of the 36 alleles showed decreased transmission (50% expected, 45.1% observed [P=.02, corrected P=.72]) at marker D11S1917. Analysis of an additional 1,702 families provided further support for negative transmission (48%) of D11S1917 allele 3 to affected offspring and positive transmission (55%) to unaffected siblings (test of heterogeneity P=3x10-4, corrected P=. 01]). A second polymorphic marker, H0570polyA, was isolated from a cosmid clone containing D11S1917, and genotyping of 2,042 families revealed strong linkage disequilibrium between the two markers (15 kb apart), with a specific haplotype, D11S1917*03-H0570polyA*02, showing decreased transmission (46.4%) to affected offspring and increased transmission (56.6%) to unaffected siblings (test of heterogeneity P=1.5x10-6, corrected P=4.3x10-4). These results not only provide sufficient justification for analysis of the gene content of the D11S1917 region for positional candidates but also show that, in the mapping of genes for common multifactorial diseases, analysis of both affected and unaffected siblings is of value and that both predisposing and nonpredisposing alleles should be anticipated.

Chromosome Mapping↗
PubMed1998

[Latent thyroid diseases in obesity].

We have investigated 2672 obese subjects (2324 females and 348 males); of these, the following two groups were considered: obese subjects with or without thyroid disease. Subjects were stratified according to age, sex, and BMI. The prevalence of thyroid disease was correlated to age, sex and BMI increased body weight. Our data showed that 22% of patients affected by essential obesity and not resident in area of iodine deficiency is affected by thyroid diseases which are not diagnosed (18%). In the obese subjects, presence of goiter is more frequent than in the normal weight subjects and affects mainly adult males. Chronic thyroiditis is typical of females (9:1 female:male ratio) with no difference between normo and overweight subjects. Prevalence of single nodule in the obese is similar to the normal weight subjects, it is more frequent in adults and in subjects with medium size obesity. However, occurrence of carcinoma (8%) in single nodules appears higher in the overweight (5-6%) as compared to the normal weight subjects.

Adenocarcinoma, Follicular↗
PubMed1998

[Thyroid tumors in obesity].

BACKGROUND: The presence of nodules in the thyroid gland is the most frequent cause of endocrinopathy. The prevalence of thyroid nodules in the United States is estimated to be between 3-10%, whereas the prevalence of thyroid nodules in European adult population is estimated to be between 4-10%. At our Clinic of Obesity, the presence of nodules in the thyroid gland of obese patients is often found, incidentally, for this reason, we decide to investigate the prevalence of this pathology in obese patients and to quatify the number of times in which the presence of nodules had not been previously diagnosed. METHODS: 3248 obese patients were examined during in the last six years (1991-1996); of these patients 747 were affected by obesity and thyropathy; of these 747 we took into consideration only those with a cold single nodule and correlated the presence of the nodule with BMI, sex and age. RESULTS AND CONCLUSIONS: The prevalence of a cold single nodule in the obese patients was 31%, of which 83% has not been previously diagnosed. Of cold nodules 8% was represented by carcinoma. The carcinoma appeared more often in females than in males (3:1). The incidence of cold nodules was more frequent in adults and in mild-medium obesity.

Adenocarcinoma, Follicular↗
PubMed1997

Insulin VNTR allele-specific effect in type 1 diabetes depends on identity of untransmitted paternal allele. The IMDIAB Group.

The IDDM2 type 1 diabetes susceptibility locus was mapped to and identified as allelic variation at the insulin gene (INS) VNTR regulatory polymorphism. In Caucasians, INS VNTR alleles divide into two discrete size classes. Class I alleles (26 to 63 repeats) predispose in a recessive way to type 1 diabetes, while class III alleles (140 to more than 200 repeats) are dominantly protective. The protective effect may be explained by higher levels of class III VNTR-associated INS mRNA in thymus such that elevated levels of preproinsulin protein enhance immune tolerance to preproinsulin, a key autoantigen in type 1 diabetes pathogenesis. The mode of action of IDDM2 is complicated, however, by parent-of-origin effects and possible allelic heterogeneity within the two defined allele classes. We have now analysed transmission of specific VNTR alleles in 1,316 families and demonstrate that a particular class I allele does not predispose to disease when paternally inherited, suggestive of polymorphic imprinting. But this paternal effect is observed only when the father's untransmitted allele is a class III. This allelic interaction is reminiscent of epigenetic phenomena observed in plants (for example, paramutation; ref. 17) and in yeast (for example, trans-inactivation; ref. 18). If untransmitted chromosomes can have functional effects on the biological properties of transmitted chromosomes, the implications for human genetics and disease are potentially considerable.

Alleles↗
PubMed1997

Evidence by allelic association-dependent methods for a type 1 diabetes polygene (IDDM6) on chromosome 18q21.

Type 1 diabetes is a common polygenic disease. Fine mapping of polygenes by affected sibpair linkage analysis is not practical and allelic association or linkage disequilibrium mapping will have to be employed to attempt to detect founder chromosomes. Given prior evidence of linkage of the Jk-D18S64 region of chromosome 18q12-q21 to type 1 diabetes, we evaluated the 12 informative microsatellite markers in the region for linkage with disease by the transmission disequilibrium test (TDT) in a UK data set of type 1 diabetic families (n = 195). Increased transmission of allele 4 of marker D18S487 to affected children was detected (P = 0.02). Support for this was extended in a total of 1067 families from four different countries by isolating, and evaluating by the TDT, two novel microsatellites within 70 kb of D18S487. Evidence for linkage and association was P = 5 x 10(-5) and 3 x 10(-4), respectively. There was no evidence for increased transmission of associated alleles to nonaffected siblings. Analysis of an additional 390 families by the TDT did not extend the evidence further, and reduced support in the total 1457 families to P = 0.001 for linkage and P = 0.003 for association. However, evidence for linkage by affected sibpair allele sharing was strong (P = 3.2 x 10(-5)) in the second data set. Heterogeneity in TDT results between data sets was, in part, accounted for by the presence of more than one common disease-associated haplotype (allelic heterogeneity) which confounds the analysis of individual alleles by the TDT. Guidelines for strategies for the mapping of polygenes are suggested with the emphasis on collections of large numbers of families from multiple populations that should be as genetically homogeneous as possible.

Adolescent↗
PubMed1997

Vitamin E and nicotinamide have similar effects in maintaining residual beta cell function in recent onset insulin-dependent diabetes (the IMDIAB IV study)

OBJECTIVE: Protection of residual beta cell function at the time of diagnosis of insulin-dependent diabetes mellitus (IDDM) by intensive insulin therapy and the addition of nicotinamide (NA) has been established. The objective of this study was to evaluate the effect of a free oxygen radical scavenger such as vitamin E (Vit E) on residual beta cell function and parameters of metabolic control in patients with recent onset IDDM undergoing intensive insulin therapy. DESIGN: The effect of Vit E was compared with that of NA (control group) in a randomized multicentre trial. METHODS: Eighty-four IDDM patients between 5 and 35 years of age (mean age 15.8 +/- 8.4 (s.d.) years) entered a one year prospective study. One group of patients (n = 42) was treated with Vit E (15 mg/kg body weight/day) for one year; the other group (n = 42) received NA for one year (25 mg/kg body weight/day). All patients were under intensive insulin therapy with three to four injections a day. Basal and stimulated (1 mg i.v. glucagon) C-peptide secretion, glycosylated haemoglobin and insulin dose were evaluated at diagnosis and at three-monthly intervals up to one year. RESULTS: Preservation and slight increase of C-peptide levels at one year compared with diagnosis were obtained in the two treated patient groups. No statistically significant differences were observed in basal or stimulated C-peptide levels between the two groups of patients for up to one year after diagnosis. Glycosylated haemoglobin and insulin dose were also similar between the two groups; however patients receiving Vit E under the age of 15 years required significantly more insulin than NA-treated patients one year after diagnosis (P < 0.04). CONCLUSIONS: Our data indicate that Vit E and NA possess similar effects in protecting residual beta cell function in patients with recent onset IDDM. Since their putative mechanism of protection on beta cell cytotoxicity is different, combination of these two vitamins may be envisaged for future trials of intervention at IDDM onset.

Adolescent↗
PubMed1997

[Comparison of results of short- and long-term therapy of obesity].

A study concerning long term results of dietetic treatment of obesity has been conducted on 1479 obese women, aged 16 to 76 years, who attended the ambulatory during the period 1992-1995. Best results in short term reduction of weight excess were found in obesity due to sedentariness or arisen after operations or emotional stress. Also, it has been noticed that percentage of subjects who went on to loose weight decreased after first year of treatment instead, percentage of subjects who grew fat increased. So, authors believe that long term therapy main object in obese people isn't loss of weight but to avoid further weight increases.

Adolescent↗
PubMed1996

Confirmation of three susceptibility genes to insulin-dependent diabetes mellitus: IDDM4, IDDM5 and IDDM8.

Previous genome-wide mapping studies have provided suggestive linkage evidence for several novel susceptibility loci responsible for insulin-dependent diabetes mellitus (IDDM); however, the evidence was not sufficient to confirm the existence of these genes. We analyzed 265 Caucasian families with IDDM and report the first evidence that meets the standard for confirmed linkage for three susceptibility loci. The maximum LOD scores (MLS) were 3.9, 4.5 and 3.6 in our data set, and 5.0, 4.6 and 5.0 for our data combined with non-overlapping data from the literature, for IDDM4 on chromosome 11q13, IDDM5 on 6q25, and IDDM8 on 6q27, respectively. However, we could not confirm linkage for IDDM3 on 15q26 and IDDM7 on 2q31-q33, or linkage disequilibrium between D2S152 and IDDM7.

Adult↗
PubMed1996

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry.

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell-mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ-specific autoimmune disease.

Abatacept↗
PubMed1996

A 5-year (1989-1993) prospective study of the incidence of IDDM in Rome and the Lazio region in the age-group 0-14 years.

OBJECTIVE: To provide data on the incidence of IDDM in Rome and the Lazio region evaluated prospectively from 1989 to 1993 for a total of > 5 million subjects younger than 15 years. RESEARCH DESIGN AND METHODS: All patients with newly discovered IDDM diagnosed between 1 January 1989 and 31 December 1993 among residents in Rome and its region were recorded. Primary ascertainment was based in diabetes clinics and specialized hospitals in the region, whereas the secondary independent source was taken from the archives of the region where patients are registered to obtain exemption from paying for medications. RESULTS: We identified 330 new patients with a degree of ascertainment of 85%. Overall the incidence rate of the disease was 7.9 per 100,000 per year (95% CI 7.1-8.8). The incidence was higher in the 5- to 9-year-old age-group (10.4 per 100,000) and in winter (36.2%). The cumulative risk for the disease is on the order of 1.18 per 1,000 subjects < 15 years of age. No significant differences in incidence were observed between boys and girls. There were 14 instances of coma at diagnosis (4.3%), but hyperglycemia without ketonuria was diagnosed in 35% of patients, suggesting an early diagnosis. DISCUSSION: Compared with the other continental Italian regions for which data are available for a single year, the IDDM incidence rate in Rome is similar. We conclude that the IDDM incidence rate in Rome and its region is comparable to that in other Southern European countries and remained stable over the 5-year observation period.

Adolescent↗
PubMed1995

Double blind trial of nicotinamide in recent-onset IDDM (the IMDIAB III study).

Nicotinamide has been recently introduced, in addition to intensive insulin therapy for patients with recent-onset insulin-dependent diabetes mellitus (IDDM) to protect beta cells from end-stage destruction. However, available data are conflicting. A double blind trial in 56 newly-diagnosed IDDM patients receiving nicotinamide for 12 months at a dose of 25 mg/kg body weight or placebo was designed in order to determine whether this treatment could improve the integrated parameters of metabolic control (insulin dose, glycated haemoglobin and C-peptide secretion) in the year after diagnosis. In addition to nicotinamide or placebo, patients received three to four insulin injections daily to optimize blood glucose levels. Patients treated with nicotinamide or placebo received similar doses of insulin during follow-up and 1 year after diagnosis with comparable glycated haemoglobin levels 6.7 +/- 1.8% nicotinamide vs 7.1 +/- 0.6% placebo). Basal and glucagon stimulated C-peptide secretion detectable at diagnosis were similarly preserved in the course of 12 months follow-up both in nicotinamide and placebo treated patients. No adverse effects were observed in patients receiving nicotinamide. When age at diagnosis was taken into account, nicotinamide treated older patients ( > 15 years of age) showed significantly higher stimulated C-peptide secretion than placebo treated patients (p < 0.02). These results suggest that nicotinamide can preserve and improve stimulated beta-cell function only in patients diagnosed after puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Linkage disequilibrium mapping of a type 1 diabetes susceptibility gene (IDDM7) to chromosome 2q31-q33.

The role of human chromosome 2 in type 1 diabetes was evaluated by analysing linkage and linkage disequilibrium at 21 microsatellite marker loci, using 348 affected sibpair families and 107 simplex families. The microsatellite D2S152 was linked to, and associated with, disease in families from three different populations. Our evidence localizes a new diabetes susceptibility gene, IDDM7, to within two centiMorgans of D2S152. This places it in a region of chromosome 2q that shows conserved synteny with the region of mouse chromosome 1 containing the murine type 1 diabetes gene, Idd5. These results demonstrate the utility of polymorphic microsatellites for linkage disequilibrium mapping of genes for complex diseases.

Adolescent↗
PubMed1995

Adjuvant therapy in recent onset type 1 diabetes at diagnosis and insulin requirement after 2 years.

Partial recovery of beta-cell function in type 1 diabetes is common after diagnosis by intensive insulin therapy. Residual beta-cell function can be improved by other therapies. Cyclosporin (CyA) and nicotinamide (NA), alone or in combination, can preserve this function, as indicated by the parameters of metabolic control (insulin dose, HbA1C). After suspension of CyA, insulin requirement returns to control values, suggesting loss of residual beta-cell function. The effects induced by withdrawal of NA after 1 year are not known. For the first time, we studied 27 type 1 diabetes patients treated with NA for 12 months and then followed up for 1 year after discontinuance of NA. Another 25 patients treated with NA + CyA and 28 control patients were followed up similarly. Insulin requirement doubled 12 months after discontinuance of NA or NA + CyA, becoming identical to that of controls. As patients showed HbA1C values similar to control subjects, it is likely that beta-cell function deteriorated after discontinuance of therapy. As NA is safer than other agents and its effects are beneficial, longer studies are warranted to investigate NA in prolonged treatments since this compound is also being considered for prevention of type 1 diabetes.

Adjuvants, Pharmaceutic↗
PubMed1994

Combination of nicotinamide and steroid versus nicotinamide in recent-onset IDDM. The IMDIAB II Study.

OBJECTIVE: The aim of this study was to compare the effect of nicotinamide (NCT) alone or in combination with a cortisone-like substance, deflazacort (DFL), on the integrated parameters of metabolic control in patients with the recent-onset of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Thirty-six patients who were diagnosed with diabetes between 5 and 35 years of age entered a randomized, double-blind, 1-year prospective study. Group A (n = 18) received NCT for 1 year (25 mg.kg-1.day-1) plus DFL for 3 months (0.6 mg.kg-1.day-1 in the first month, 0.3 mg.kg-1.day-1 in the other 2 months). Group B (n = 18) received NCT for 1 year (25 mg.kg-1.day-1) plus placebo for the first 3 months. All patients were treated with intensified insulin therapy. RESULTS: At 3 months after diagnosis, the insulin dose was significantly higher in group A compared with group B (P < 0.03) with similar HbA1 levels. Basal and stimulated C-peptide levels in group A of both adults and children were significantly higher compared with patients of group B (P < 0.05 and P < 0.03, respectively). At the end of a 1-year follow-up, basal C-peptide did not differ between the two groups, although stimulated C-peptide was still significantly higher in patients of group A compared with group B (P < 0.05). Finally, insulin requirement did not differ between the two groups. CONCLUSIONS: A short-term course of DFL therapy at diagnosis in addition to NCT slightly increases glucagon-stimulated but not basal beta-cell function after 1 year.

Adolescent↗
PubMed1993

IDDM and rainfall.

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Diabetes Mellitus, Type 1↗