OBJECTIVE -The aim of the present study was to define heterogeneity of adult-onset autoimmune diabetes based on characterization of GAD antibodies (GADAs). RESEARCH DESIGN AND METHODS-Patients enrolled in a nationwide survey, the Non Insulin Requiring Autoimmune Diabetes (NIRAD) Study, have been screened for GADAs and IA-2 antibodies (IA-2As) and further characterized for GADA titer, antibodies to thyroid peroxidase (TPO), and HLA DRB1-DQB1 polymorphisms.RESULTS -Of 4,250 consecutive type 2 diabetic patients, 4.5% had either GADAs and/or IA-2As. Patients with autoimmune diabetes showed a clinical phenotype significantly different from that of type 2 diabetes, including higher fasting glucose and A1C, lower BMI and uric acid, lower prevalence of metabolic syndrome and its components, and higher frequency of TPO antibodies. More interestingly, analysis of GADA titers showed a bimodal distribution that identified two subgroups of patients with high (Ͼ32 GADA arbitrary units) and low (Յ32 GADA arbitrary units) GADA titers. Compared with those with low GADA titers, patients with high GADA titers had more prominent traits of insulin deficiency and a profile of more severe autoimmunity resulting in higher A1C, lower BMI, a lower prevalence of metabolic syndrome and its components (P Ͻ 0.02 for all), a higher prevalence of IA-2As, TPO antibodies (P Ͻ 0.003 for both), and DRB1*03-DQB1*0201 (50 vs. 26.8%, P ϭ 0.001), and a decreasing frequency of DQB1*0602 and DRB1*0403 (from type 2 to low and to high GADA titer autoimmune diabetes; P Ͻ 0.001 for trend for both comparisons).CONCLUSIONS -GADA titers identify two subgroups of patients with adult-onset autoimmune diabetes having distinct clinical, autoimmune, and genetic features. Diabetes Care 30:932-938, 2007

Objective: The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up. Methods: This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression. Results: During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes (P!0.0001 for both). A BMI of %25 kg/m 2 and IA-2 IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (P!0.0001 for both). The proportion of LADA patients requiring insulin was significantly higher in the group of subjects treated also with sulfonylurea in the first year from diagnosis compared with those treated with diet and/or insulin sensitizers (P!0.001). The multivariate analysis confirmed that the presence of high GADA titer was a significant predictor of insulin requirement (P!0.0001, ORZ6.95). Conclusions: High GADA titer, BMI % 25, ZnT8 and IA-2 IC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients.

Aims We previously demonstrated the presence of two different populations among adult-onset autoimmune diabetes (latent autoimmume diabetes of adults; LADA) having high or low titre of antibodies to glutamic acid decarboxylase (GADA). The transcription factor 7-like 2 (TCF7L2) gene has been recognized as the major gene associated with Type 2 diabetes. The aim of the present study was to evaluate whether the phenotypic heterogeneity of LADA based on GADA titre is associated with TCF7L2 polymorphisms.Methods Two hundred and fifty patients identified as LADA, divided into two subgroups with low (£ 32 arbitrary units) or high (> 32 units) GADA titre, 620 subjects with Type 2 diabetes [from the Non-Insulin Requiring Autoimmune Diabetes (NIRAD) study cohort of 5330 subjects] in addition to 551 consecutive cases of Type 1 diabetes and 545 normoglycaemic subjects were analysed for the rs12255372 and rs7903146 polymorphisms of the TCF7L2 gene using Taqman.Results The genotype and allele distributions of the two polymorphisms revealed similar frequencies in subjects with low GADA titre and Type 2 diabetes. High GADA titre, Type 1 diabetes and controls also showed comparable frequencies. A significant increase of GT ⁄ TT genotypes of the rs12255372 single-nucleotide polymorphism (SNP) and CT ⁄ TT genotypes of the rs7903146 SNP was observed in low GADA titre and Type 2 diabetes compared with high GADA titre, Type 1 diabetes and controls (P £ 0.04 for both comparisons). The risk alleles of both variants were increased in low GADA titre and Type 2 diabetes compared with high GADA titre, Type 1 diabetes and control subjects (P < 0.02 for all comparisons).Conclusions TCF7L2 common genetic variants of susceptibility are associated only with low GADA antibody titre in LADA patients.Diabet. Med. 27, 701-704 (2010)

We identified the second novel pathogenic mutation in LMF1 gene in a patient with severe hypertriglyceridemia. LPL deficiency in our patient was milder than in the carrier of the Y439X previously described.

Our data confirm the high association rate of AG in ATD which frequently is not an isolated disease but configure the picture of APS type III and need to be followed accordingly. An early diagnosis may be useful for diagnosis of gastric carcinoids and to explain and treat a gastric related L-thyroxine malabsorption and presence of chronic unexplained anemia.