DIAGNOSTIC HETEROGENEITY OF DIABETES IN LEAN YOUNG-ADULTS - CLASSIFICATION BASED ON IMMUNOLOGICAL AND GENETIC-PARAMETERS

The aim of our study was to investigate the relative prevalence of the different forms of diabetes in young adults and their respective clin ical characteristics. Included were 51 nonobese patients (BMI < 27 kg/ m(2)) with diabetes diagnosed before age 40, excluding typical IDDM. E ach patient was subjected to screening for glucokinase gene (MODY2) an d mitochondrial DNA (at nucleotide 3243) mutations, to HLA class II ge notyping, and screening for the presence of islet cell antibodies (ICA s) and anti-GAD antibodies. Informative families were analyzed for lin kage of diabetes to chromosome 12q (MODY3). Based on clinical criteria , patients were subdivided into MODY (n = 19) and non-MODY (n 32). In the MODY group, we identified three patients with MODY2, one with the 3243 mitochondrial mutation, and another with autoimmune diabetes. One of the five MODY families available for Linkage study was shown to ha ve MODY3. In the non-MODY group, we found five patients with autoimmun e diabetes and one with MODY2. No clinical parameter was helpful to cl assify patients in one of these subclasses of diabetes; however the gl ucagon-stimulated C-peptide was useful to discriminate between MODY2 p atients and the others. In conclusion, young and lean non-insulin-depe ndent diabetic patients constitute a very heterogeneous group, althoug h they present similar clinical characteristics. The clinical distinct ion of MODY and non-MODY patients allows correct classification in, at most, 75% of the patients and thus is not sufficient to predict clini cal course. However, immunological and genetic parameters allowed us t o classify only 25% of the patients in specific diagnostic classes.