Clinical, immunological, and genetic heterogeneity of diabetes in an Italian population-based cohort of lean newly diagnosed patients aged 30-54 years

OBJECTIVE - In lean diabetic patients, the presentation of the disease does not allow one to easily distinguish between type 1 and type 2. Aims of this study were to describe clinical, immunological, and genetic features of lean newly diagnosed diabetic patients. RESEARCH DESIGN AND METHODS - A population-based cohort of 130 lean (BMI <25 kg/m(2)) newly diagnosed patients, aged 30-54 years, was identified among residents of the province of Turin. Islet cell antibodies (ICAs), anti-CAD, fasting and glucagon-stimulated C-peptide values, and HLA DQA1-DQB1 susceptibility genotypes were assessed within 2 months of the diagnosis. RESULTS - A total of 45 (34.6%) and 29 (22.3%) patients were, respectively, ICA(+) and anti-GAD(+), with 15 (11.5%) having both antibodies. In 59 patients, ICAs and/or anti-CAD antibodies were detected, giving a high prevalence of autoimmunity (45.4%, 95% CI 36.8-54.0); relative to patients without markers (n = 71), they were younger (40.8 +/- 7.5 vs. 45.0 +/- 6.5 years, P < 0.001) and showed lower values of fasting C-peptide (0.56 +/- 0.33 vs. 0.79 +/- 0.41 nmol/l, P < 0.001) and stimulated C-peptide (1.03 +/- 0.56 vs. 1.42 +/- 0.69 nmol/l, P < 0.001). The lowest stimulated C-peptide values were found in patients with both ICA and anti-CAD antibodies. Frequencies of adult-onset. type 1 and type 2 diabetes were, respectively 49.2 and 50.8%. Clinical and genetic features were not useful in the classification of patients. CONCLUSIONS - Almost 50% of lean young and middle-aged patients were ICA(+) and/or anti-GAD(+), suggesting a high prevalence of a slowly evolving form of type 1 diabetes. The evaluation at diagnosis of both beta-cell secretory capacity and markers of autoimmunity is recommended to provide a pathogenetic classification of the disease.