Autoantibody negative new onset type 1 diabetic patients lacking high risk HLA alleles in a caucasian population: are these type 1b diabetes cases?

Background: In Caucasians, a small number of Type 1 diabetic patients do not show evidence of humoral islet autoimmunity at disease onset, at least with common screening procedures. In African- and Hispanic-American diabetic children at time of diagnosis, many show no evidence of autoimmunity but have an atypical clinical form of the disease. According to the recent American Diabetes Association classification, this subgroup of autoantibody negative patients is referred to as Type 1b diabetic subjects.

A multi-centre randomized trial of two different doses of nicotinamide in patients with recent-onset type 1 diabetes (the IMDIAB VI).

Background: Intensive insulin therapy is the gold standard by which Type 1 diabetes is treated. In addition to this therapy, administration of nicotinamide (NA) can be beneficial. This concept is reinforced by the results of a recent meta-analysis of the use of NA in patients with recent-onset Type 1 diabetes.

Metabolic and immune parameters at clinical onset of insulin-dependent diabetes: a population-based study. IMDIAB Study Group. Immunotherapy Diabetes.

The age at diagnosis of insulin-dependent diabetes mellitus (type I DM) varies between childhood and adulthood. The aim of this study was to define the immunologic and metabolic characteristics of the disease according to the age at which it is diagnosed. We evaluated the residual beta-cell function (basal and stimulated C-peptide) and frequency of two major islet cell-related autoantibodies, glutamic acid decarboxylase (GAD) and tyrosine phosphatase-like molecule (IA-2ic), at the onset of type I DM.

[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.

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.

Dissecting the genetics of type 1 diabetes: relevance for familial clustering and differences in incidence.

A combination of genetic and environmental factors is most likely the cause of Type 1 diabetes. Results from twin data, familial clustering of the disease and difference in incidence according to ethnicity infer the presence of specific disease genes. The genetic component of Type 1 diabetes cannot be classified according to a classical model of inheritance but is due to an interaction between different genes and environmental factors.

[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.

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.

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.

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.

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).

[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.

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).

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.

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.

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.

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).

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.