Latent Autoimmune Diabetes in Adults Differs Genetically From Classical Type 1 Diabetes Diagnosed After the Age of 35 Years

Abstract

OBJECTIVE We studied differences between patients with latent autoimmune diabetes in adults (LADA), type 2 diabetes, and classical type 1 diabetes diagnosed after age 35 years. RESEARCH DESIGN AND METHODS Polymorphisms in HLA-DQB1, INS, PTPN22, and CTLA4 were genotyped in patients with LADA (n = 213), type 1 diabetes diagnosed at >35 years of age (T1D>35y; n = 257) or <20 years of age (T1D<20y; n = 158), and type 2 diabetes. RESULTS Although patients with LADA had an increased frequency of HLA-DQB1 and PTPN22 risk genotypes and alleles compared with type 2 diabetic subjects, the frequency was significantly lower compared with T1D>35y patients. Genotype frequencies, measures of insulin secretion, and metabolic traits within LADA differed according to GAD antibody (GADA) quartiles, but even the highest quartile differed from type 1 diabetes. Having two or more risk genotypes was associated with lower C-peptide concentrations in LADA. CONCLUSIONS LADA patients differed genetically and phenotypically from both T1D>35y and type 2 diabetic patients in a manner dependent on GADA levels.