No Relation Between Cystic Fibrosis–Related Diabetes and Type 1 Diabetes Autoimmunity

D iabetes is the most common co-morbidity in individuals with cystic fibrosis. The etiology is poorly understood. Data on the presence of diabetes autoantibodies are conflicting, and little is known about type 1 diabetes gene associations. Our goal was to determine the prevalence of antibodies and HLA haplotypes known to be associated with type 1 diabetes in cystic fibrosis–related diabetes (CFRD). Patients with CFRD with fasting hyper-glycemia were recruited from the University of Minnesota. Serum for antibodies and buffy coats for HLA were sent for analysis to the Barbara Davis Center for Childhood Diabetes (BDC). All patients gave informed consent. The Eisenbarth laboratory at BDC serves as the autoantibody/HLA reference laboratory for large national diabetes studies. Insulin, insulinoma-associated protein 2 (IA-2), GAD65, and zinc transporter 8 (ZnT8) autoantibodies were measured by radioimmunoassay (1,2). HLA class II al-leles were determined for DQB1 loci (3). Comparison data were obtained from new-onset diabetes and population studies collected at BDC (1–3). Of 76 CFRD patients, 50% were female, the average age was 34 years (range 15–55), and the average duration of diabetes was 10 years (range 1–33). All received constant or intermittent insulin therapy. In the general population, ;2% of individuals are positive for one of IA-2, GAD, ZnT8, or insulin autoantibodies (1). In contrast, 55–98% of individuals with type 1 diabetes are positive for at least one of these autoantibodies (2). Only 5% of CFRD patients had autoantibodies, including three subjects with antibodies to GAD and one subject with antibodies to IA-2. Insulin administration itself induces insulin antibodies, which were found in 32% of CFRD patients. Thirty-six percent of CFRD patients had high-risk alleles compared with 47% of the general population and more than 90% of those with type 1 diabetes (3). Seventeen percent of CFRD patients were DR31, 14% DR41, and 5% DR31/DR41. The etiology of CFRD is poorly understood and probably multifactorial. The primary defect is insulin insufficiency. Pancreatic fibrosis leads to ;50% reduction in islet mass. However, the correlation between the degree of islet destruction and clinical diabetes is poor, leading to speculation that there are other factors causing diabetes, including autoimmunity. Because these CFRD patients all had fasting hyperglycemia, they represent the severe end of the glucose intolerance spectrum and might be the most likely to exhibit associations with type 1 diabetes. Although autoantibody levels can drop after diagnosis and subjects in this study may have had diabetes for …