A Clinical Screening Tool Identifies Autoimmune Diabetes in Adults: Part 3

RESEARCH DESIGN AND METHODS

Retrospective study

Patients with LADA (n = 102) and type 2 diabetes (n = 111) were recruited from metropolitan Melbourne by referral from diabetes educators in community centers and treating physicians and through the Royal Melbourne Hospital diabetes clinics. A majority (97%) of the subjects were Caucasian. All patients (aged 30–75 years) had diabetes according to World Health Organization criteria (14). Patients with LADA were distinguished from type 1 diabetic patients because they had no requirement for insulin at diagnosis and for a minimum of 6 months after diagnosis. Subjects with LADA were distinguished from type 2 diabetic patients because they were serum GADA+, whereas type 2 diabetic subjects were GADA−. Other islet autoantibodies, namely IAAs and IA-2As, were not tested for at entry into the study because of their reported low frequency in LADA. Subjects known to have secondary forms of diabetes were excluded. All subjects underwent a structured interview (appendix) to retrospectively determine the clinical features of presentation. The study was approved by the Royal Melbourne Hospital Human Research and Ethics Committee and subjects participating provided written informed consent.
Prospective study

Subsequently, a prospective study was performed on 130 subjects (aged 30–75 years) with recently diagnosed (<2 months) diabetes according to World Health Organization criteria who did not require insulin treatment. Subjects were recruited from a national diabetes register, the National Diabetes Services Scheme, which is managed by Diabetes Australia. Subjects registering with the National Diabetes Services Scheme have the option of agreeing to be contacted for the purpose of research. All subjects eligible for the study (i.e., aged 30–75 years, who did not require insulin at diagnosis) were sent a letter inviting them to participate in the study. Subjects who agreed to participate in the study provided written consent. After a structured interview, patients had blood taken to determine GADAs. The study was approved by the Royal Melbourne Hospital Clinical Research and Ethics Committee.
GADA assay

GADAs were measured by precipitation of in vitro–transcribed and –translated [35S]methionine-labeled GAD65. The assay has had good sensitivity and specificity in International Workshops and Standardization Programs conducted by the Immunology of Diabetes Society (e.g., in ref. 15). Specificity and sensitivity in the 2003 Diabetes Antibody Standardization Program were 97 and 80%, respectively. The threshold for GADA positivity was established as the 97th percentile of unselected healthy schoolchildren at 5 units/ml.