CLINICAL STUDY Clinical phenotype and b-cell autoimmunity in Italian patients with adult-onset diabetes S Genovese, E Bazzigaluppi 2 , D Gonc ¸alves, A Ciucci, M G Cavallo 3 , F Purrello 4 , M Anello 4 , C M Rotella 5 , G Bardini 5 , O Vaccaro 6 , G Riccardi 6 , P Travaglini, E Morenghi, E Bosi 2 and P Pozzilli 1 Endocrinology and Diabetes Unit and Biometrical Unit, Istituto Clinico Humanitas IRCCS, via Manzoni, 56, 20089 Rozzano, Milan, Italy, 1 Department of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy, 2 General Medicine, Diabetes and Endocrinology Unit, Vita-Salute San Raffaele University Hospital and Laboraf, Diagnostica e Ricerca San Raffaele, Milan, Italy, 3 Department of Medical Therapeutics, University of Rome ‘La Sapienza’, Rome, Italy, 4 Internal Medicine, Cannizzaro Hospital, University of Catania, Catania, Italy, 5 Department of Endocrinology and Metabolic Diseases, University of Florence, Florence, Italy and 6 Institute of Internal Medicine and Metabolic Diseases, University Federico II, Naples, Italy (Correspondence should be addressed to S Genovese; Email: stefano.genovese@humanitas.it.) Abstract Objective: To characterize the phenotype of a large population of Italian patients with adult onset ($ 40 years) diabetes who were attending outpatient clinics and who were screened for glutamic acid decarboxylase 65 autoantibodies (GADA), protein tyrosine phosphatase IA-2 (IA-2A) and IA- 2b/phogrin (IA-2bA). Design and methods: This was a cross-sectional study comprising a total of 881 patients, aged # 70 years, diagnosed with type 2 diabetes after the age of 40 years, and consecutively recruited in five clinics located in different geographic areas of Italy (Milan, Florence, Rome, Naples and Catania). Their mean disease duration was 8.1 (6.9; S.D. ) years. GADA, IA-2A and IA-2bA were measured with radiobinding assays with in vitro translated S-methionine-labelled glutamic acid decarboxylase 65 (GAD65) or IA-2 or IA-2b. Anthropometric and clinical data were collected and compared amongst patients with or without autoantibodies. Results: Sixty-three (7.1%) patients had one or more autoantibodies, 58 (6.6%) had GADA, 22 (2.5%) had IA-2A, six (0.7%) had IA-2bA and 19 (2.15%) had two or more autoantibodies. IA-2A or IA-2bA, in the absence of GADA, were found in only five patients. Autoantibody-positive patients were more often female (63.5 vs 36.5%; P , 0.009), had higher glycated haemoglobin (Hb A1c) (P , 0.001), lower body mass index (BMI; P , 0.0005) and waist/hip ratio (WHR; P , 0.01); female gender being the main contributor to BMI and WHR. We did not observe any differences in age at diagnosis or duration of disease with respect to the presence or absence of islet autoantibodies. The proportion of patients on insulin therapy was higher in patients with two or more antibodies, compared with those with one antibody only, and no antibodies (P for trend , 0.001), and among patients with GADA, in those with higher antibody titre (73.9% in those with . 10 units vs 42.0% in those with # 10 units; P , 0.007). Conclusions: Patients with adult onset diabetes characterized by autoimmunity to b-cells showed a clinical phenotype with anthropometric features that differed from those classically observed in patients with type 2 diabetes. The number and titre of autoantibodies, which reflect the severity of autoimmunity and b-cell impairment, amplified this difference. The usefulness of autoantibody screening in adult-onset diabetes is further emphasized by these findings. European Journal of Endocrinology 154 441–447 Introduction A proportion of adult patients diagnosed with type 2 diabetes develops insulin-requiring diabetes during follow-up and many of these can be identified by the presence of circulating islet autoantibodies. This form of diabetes is also referred to as latent autoimmune diabetes in adults (LADA) (1–3) and according to the last classification criteria is now considered a form of type 1 diabetes (4). Autoimmune diabetes is characterized by the pre- sence of one or more islet-specific autoantibodies, including islet cell autoantibodies (ICA), insulin (IAA) and autoantibodies directed against the three major European Journal of Endocrinology (2006) 154 441–447 ISSN 0804-4643 q 2006 Society of the European Journal of Endocrinology DOI: 10.1530/eje.1.02115 Online version via www.eje-online.org