This study aimed to determine the prevalence of
antibodies against
glutamic acid decarboxylase (anti-GAD) and islet cell
antibodies (ICA) in relation to beta-cell function in adults newly-diagnosed with
diabetes mellitus. beta-cell function was assessed in adults aged 25-70 years newly-diagnosed with
diabetes mellitus (n = 84) and control subjects (n = 34) using a 1.6 MJ mixed meal test procedure. beta-cell function was evaluated by the true
insulin (defined as immunoreactive
insulin minus
proinsulin) response to the mixed meal test. Subjects were classified on the basis of the area under the true
insulin curve (normal 16830-107700 pmol min/I) and the sum of the 30 and 60 min incremental response (normal 285-3295 pmol/I). The prevalence of anti-GAD and ICA was determined using radioimmunoprecipitation and indirect immunofluorescence, respectively. Twelve (14%) of the study cohort were
insulin deficient showing little or no true
insulin release. Of the
insulin deficient individuals, seven (58%) subjects were anti-GAD antibody positive, compared with eleven (15%) of the subjects without
insulin deficiency (P < 0.001). Seven (58%)
insulin deficient subjects were ICA positive, whereas only two (3%) non-
insulin deficient subjects were ICA positive (P < 0.001). Eight (67%) of the
insulin deficient individuals had anti-GAD or ICA, compared with twelve (17%) of those who were not
insulin deficient (P < 0.001). The positive predictive values for
insulin deficiency of anti-GAD and ICA were 39 and 78% respectively. The sensitivity of both
antibodies for detecting
insulin deficiency was 50%. The specificity for detecting
insulin deficiency was 85% for anti-GAD and 97% for ICA. Positivity for both anti-GAD and ICA gave a specificity and positive predictive value for
insulin deficiency of 99%, and a sensitivity of 50%. Nearly one in seven adults presenting with
diabetes mellitus as a new diagnosis are
insulin deficient using our criteria. Loss of beta-cell function in two thirds of individuals who are
insulin deficient can be identified by anti-GAD and ICA. Early detection of these
immune markers of beta-cell damage creates the potential for immune modulation to limit such damage.