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We studied the independent influence of sex, age and islet-cell antibodies (ICA) on residual beta-cell secretion and metabolic control during the first year after the diagnosis of type 1 diabetes mellitus in 40 consecutive newly diagnosed patients. Glucagon-stimulated C-peptide secretion was measured after 5-10 days and 3, 6 and 12 months of diagnosis. ICA (JDF units) and complement-fixing ICA (CF-ICA) were determined at diagnosis and after 12 months. The influence of sex, age and ICA was analyzed in a multivariate analysis of variance of 3 factors (age, sex and ICA) for repeated measures over time. ICA and CF-ICA were positive in 75.0% and 35.0% of patients at diagnosis and in 48.7% and 20.5% of patients one year later. Persistence of ICA positivity was higher in females (p. less than 0.001) and in CF-ICA+ patients (p less than 0.01), but did not involve a different evolution of C-peptide secretion. Males had a lower C-peptide secretion than females (p = 0.023) during the first year after the diagnosis of type 1 diabetes, independently of the age and ICA status of the patients. Adult patients (greater than or equal to 18 years-old) had lower HbA1 values than younger patients (p = 0.006) and ICA+ patients with a moderate or high value (greater than 10 JDF units) had a lower C-peptide secretion over time (p = 0.031 at 6 months, p = 0.067 at 12 months) and higher HbA1 values (p = 0.056) than younger patients. HbA1 was significantly explained by ICA and C-peptide values in a stepwise multiple regression analysis (p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)