Genetic Similarities Between Latent Autoimmune Diabetes and Type 1 and Type 2 Diabetes

In this issue of Diabetes , Cervin et al. (1) investigated whether patients with latent autoimmune diabetes in adults (LADA) (defined as age at diabetes onset >35 years, GADA positive), analyzing known risk alleles for type 1 and type 2 diabetes, share genetic polymorphisms with type 1 diabetes (age at onset 35 years, GADA negative). In their LADA patients, they confirmed an increased frequency of type 1 diabetes–associated genetic risk factors including the heterozygous HLA-DQB1\*0201/\*0302 genotype, insulin AA genotype (rs689), and increased CT and TT genotypes of the PTPN22 gene (rs2476601) (2). Somewhat surprisingly, in LADA patients they also found a higher frequency of the type 2 diabetes–associated CT and TT genotypes of the TCF7L2 gene (rs7903146) (3), therefore concluding that LADA shares genetic features with both type 1 and type 2 diabetes. The article by Cervin et al. (1) uses the term LADA and immediately abandons the standard meaning of the term, instead equating LADA with GAD-positive patients who developed diabetes after age 35 years. LADA has been defined as the presence of GAD antibodies in patients with age of onset of diabetes after 35 years and insulin independence for at least 6 months after diagnosis (4–6). We agree with the authors in abandoning the standard definition of LADA and would agree with a number of other reviews that suggest one should abandon the term LADA altogether (7,8). A simpler alternative would be islet autoantibody–positive diabetes, which would likely come close to equating with type 1A diabetes, depending upon the …