SLOW METABOLIC DETERIORATION TOWARDS DIABETES IN ISLET-CELL ANTIBODY-POSITIVE PATIENTS WITH AUTOIMMUNE POLYENDOCRINE DISEASE

We studied metabolic progression to IDDM in a cohort of adults who are ICA-positive and have associated autoimmune endocrine disease or circ ulating organ-specific autoantibodies (the Polyendocrine Study). Of th e 186 individuals recruited 27 developed overt diabetes after a median follow-up of 4.5 years (range 0.4-12). Of these, eight patients did n ot require insulin treatment until at least 6 months after clinical di agnosis, with an interval of 1.8 years (1.2-5.7) . An IVGTT was perfor med in 38 subjects and 23 had sequential studies. Of the initial 38 su bjects six developed diabetes and only three showed a loss of FPIR to glucose (below the first percentile of a normal control group) before clinical onset of the disease. An additional three subjects showed a l oss of the FPIR, and all still have normal glucose tolerance after med ian follow-up of 28 months (22-95). A ''whole'' or ''mixed'' pattern o f islet cell staining was found in five of the six patients who develo ped diabetes and antibodies against an islet 37 k- antigen were detect able in four patients, all of whom required insulin soon after diagnos is. A beta-cell ''selective'' ICA staining pattern was seen in 14 of 1 7 subjects who did not develop diabetes and the ''mixed'' pattern in o nly three. None of this group had detectable 37 k-antibodies. We concl ude that metabolic deterioration is slow in polyendocrine patients, an d that the IVGTT has less prognostic significance in this group than i n first degree relatives of patients with IDDM. In contrast, the prese nce of the ''whole'' or ''mixed'' ICA staining pattern or of 37k-antib odies can identify a high risk of progression to IDDM within this poly endocrine population and may indicate the rate of metabolic deteriorat ion.