ISLET-CELL ANTIBODIES AND ANTIBODIES AGAINST GLUTAMIC-ACID DECARBOXYLASE IN NEWLY-DIAGNOSED ADULT-ONSET DIABETES-MELLITUS

This study aimed to determine the prevalence of antibodies against glu tamic acid decarboxylase (anti-GAD) and islet cell antibodies (ICA) in relation to beta-cell function in adults newly-diagnosed with diabete s 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 m inus proinsulin) response to the mixed meal test. Subjects were classi fied on the basis of the area under the true insulin curve (normal 16 830-107 700 pmol min/l) and the sum of the 30 and 60 min incremental r esponse (normal 285-3295 pmol/l). The prevalence of anti-GAD and ICA w as determined using radioimmunoprecipitation and indirect immunofluore scence, respectively. Twelve (14%) of the study cohort were insulin de ficient showing little or no true insulin release. Of the insulin defi cient individuals, seven (58%) subjects were anti-GAD antibody positiv e, compared with eleven (15%) of the subjects without insulin deficien cy (P < 0.001). Seven (58%) insulin deficient subjects were ICA positi ve, whereas only two (3%) non-insulin deficient subjects were ICA posi tive (P < 0.001). Eight (67%) of the insulin deficient individuals had anti-GAD or ICA, compared with twelve (17%) of those who were not ins ulin deficient (P < 0.001). The positive predictive values for insulin deficiency of anti-GAD and ICA were 39 and 78% respectively. The sens itivity of both antibodies for detecting insulin deficiency was 50%. T he specificity for detecting insulin deficiency was 85% for anti-GAD a nd 97% for ICA. Positivity for both anti-GAD and ICA gave a specificit y and positive predictive value for insulin deficiency of 99%, and a s ensitivity 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 insul in deficient can be identified by anti-GAD and ICA. Early detection of these immune markers of beta-cell damage creates the potential for im mune modulation to limit such damage.