Beta-cell cytoadherent lymphocytes in some subjects at risk for type 1 (insulin-dependent) diabetes: progression to diabetes within 2 years.

The increased binding in vitro of CD3 CD4 T-lymphocytes from type 1 (insulin-dependent) diabetic patients to beta-cell membrane antigens compared to lymphocytes from control subjects was previously shown to be a marker of cell-mediated immunity, called diabetic rosettes. In the present study diabetic rosettes were detected in some subjects at risk for type 1 diabetes (first degree relatives of type 1 diabetic patients or nondiabetic subjects with previous transient hyperglycaemia). The mean number of lymphocytes adherent to beta-cells (beta-CL) was significantly higher in subjects at risk for type 1 diabetes than in age- and sex-matched control blood bank donors (P less than 10(-6]. This number of beta-CL was higher in type 1 diabetic patients than in subjects at risk (P less than 10(-6], and one-way analysis of variance by rank (Kruskal-Wallis) revealed that the three populations (controls, diabetics, and risk subjects) were different in terms of beta-CL values (P less than 0.001). The percentage of subjects at risk that had a positive test (arbitrarily defined as a beta-CL value higher than the 95th percentile of 228 controls) was 20%. No difference was observed between the two subgroups of subjects at risk in terms of either mean +/- SEM of beta-CL or percentages of individuals with a positive test. These diabetic rosettes were slightly associated with acute insulin response to iv glucose lower than the 5th percentile of controls (immunoreactive insulin at 1 +/- 3 min, 250 pmol/L; by chi 2, P = 0.04) and with HLA DR 3/4 heterozygosity (by chi 2, P = 0.04). They were not associated with islet cell antibodies (regardless of the threshold for positivity, expressed in Juvenile Diabetes Foundation units), insulin autoantibodies, activated (HLA DR+) T-lymphocytes, or sex. A statistical association was detected between HLA DR 3/4 heterozygosity and a low acute insulin response to iv glucose (by chi 2, P less than 0.003). The preliminary (2-yr) longitudinal follow-up revealed that out of five islet cell antibody-positive subjects who progressed to type 1 diabetes, three displayed beta-CL values higher than the 90th percentile of controls. Diabetic rosettes could, thus, be detected in some individuals at risk for type 1 diabetes as a marker of cell-mediated immunity.