Adult-Onset Atypical (Type 1) Diabetes Additional insights and differences with type 1A diabetes in a European Mediterranean population

OBJECTIVE — In 1997, the American Diabetes Association proposed two subcategories for type 1 diabetes: type 1A or immunomediated diabetes and type 1B or idiopathic diabetes characterized by negative -cell autoimmunity markers, lack of association with HLA, and fluctuating insulinopenia. The aim of this study was to examine clinical characteristics, -cell function, HLA typing, and mutations in maturity-onset diabetes of the young (MODY) genes in patients with atypical type 1 diabetes (type 1 diabetes diagnosed at onset, without pancreatic autoantibodies and fluctuating insulinopenia). RESEARCH DESIGN AND METHODS — Eight patients with atypical type 1 diabetes (all men, 30.7 7.6 years) and 16 newly diagnosed age- and sex-matched patients with type 1A diabetes were studied retrospectively. Islet cell, GAD, tyrosine phosphatase and insulin antibod-ies, and basal and stimulated plasma C-peptide were measured at onset and after 1 year. HLA-DRB1-DQA1-DQB1 typing and screening for mutations in the HNF-1 and HNF-4 genes were performed from genomic DNA. RESULTS — Atypical patients displayed significantly higher BMI and better -cell function at onset and after 12 months. Three patients carried protective or neutral type 1 diabetes haplo-types, five patients displayed heterozygosity for susceptible and protective haplotypes, and seven patients showed Asp57. We found a nondescribed variant Pro436Ser in exon 10 of the HNF-4 gene in one atypical patient without susceptible haplotypes. CONCLUSIONS — In our population, there are atypical forms of young adult–onset keto-sis-prone diabetes initially diagnosed as type 1 diabetes, differing from type 1 diabetes in the absence of -cell autoimmunity, persistent -cell function capacity, fluctuating insulin require-ments and ketosis-prone episodes, as well as clinical features of type 2 diabetes. Only one subgroup could be strictly classified as having type 1B diabetes. Additional information is still needed to improve our understanding of the mechanisms that finally lead to the disease