Soluble CD8 antigen, stimulated C-peptide and islet cell antibodies are predictors of insulin requirement in newly diagnosed patients with unclassifiable diabetes.

To evaluate the predictive factors of insulin requirement in newly diagnosed patients with unclassifiable diabetes, 54 consecutive patients, aged less than 35 years, were prospectively followed for 3 years or more. At entry, haemoglobin HbA1c, basal and stimulated C-peptide concentrations, HLA phenotype, islet cell antibodies (ICA) status, and serum levels of soluble CD8 antigen (sCD8) were evaluated. After a median time of 9 (range 2-32) months, 31 patients (group 1) required insulin therapy, whereas 23 patients (group 2) remained non-insulin-requiring after 36 months. Group 1 patients were younger (P < 0.05) and had higher HbA1c and sCD8 serum levels (P < 0.0001), respectively), a higher frequency of ICA positivity and of HLA DR3 and/or DR4 phenotype (P < 0.005 and P < 0.0001, respectively), and lower C-peptide concentrations (P < 0.005 and P < 0.0001, basal and stimulated, respectively) than group 2. The sensitivity, specificity, positive and negative predictive value, and overall accuracy for the subsequent insulin requirement were: sCD8 serum levels (> 737 U/ml), 100%, 65%, 79%, 100% and 85%, respectively; stimulated C-peptide (< 0.60 nmol/l), 71%, 96%, 96%, 74% and 81%, respectively; and ICA positivity (> 20 JDFU), 45%, 91%, 87%, 55% and 65%, respectively. Thus, higher sCD8 serum levels, low stimulated C-peptide concentrations and ICA positivity are the most powerful predictors of subsequent recourse to insulin therapy in young, newly detected patients with unclassifiable diabetes.