To learn more about the preclinical phase of IDDM we observed for a median period of 46.5 months (range 0.5-69 months) a group of 57 siblings positive for ICA and/or IAA when first screened within 6 months of the diagnosis of the proband. Sequential blood samples and IVGTTs were obtained at intervals of 6-12 months. Seventeen siblings (29.8 %) presented with IDDM during the observation period. The duration of the known preclinical period ranged from 0.5 to 51 months (median 29 months). The converters were younger than the other siblings (P < 0.05) and had higher initial ICA levels (P < 0.01). In addition they had a lower FPIR in the first IVGTT (P < 0.001). On all subsequent tests the converters had higher ICA levels and a lower FPIR (P < 0.05 or less), a lower glucose elimination rate from the third test onwards (P < 0.01 or less) and higher IAA levels at 3 years (P < 0.05). Some variation could be observed in the FPIR in the converters with an initial increase and subsequent decrease (P < 0.05 for both). Their levels of complement-fixing ICA increased up to 18 months (P< 0.05) and IAA levels up to 3 years (P< 0.01). Those high risk siblings who progress to clinical IDDM are characterized by young age, strong and increasing signs of islet-cell specific autoimmunity, reduced insulin secreting capacity and emerging glucose intolerance. The present observations seem to be incompatible with the hypothesis of beta-cell destruction occurring at a constant, predictable rate. [Diabetologia (1994) 37: 388-393] Key words Preclinical IDDM, islet cell antibodies, early insulin response, glucose elimination rate.
Insulin-dependent diabetes mellitus (IDDM) is now perceived as an autoimmune disease characterized by progressive beta-cell destruction during an asymptomatic preclinical phase [1,2]. The duration of this preclinical phase apparently varies considerably, since the disease may be diagnosed both in infancy and in old age * See Acknowledgements