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 Tlymphocytes from type 1 (insulin-dependent) diabetic patients to β-cell membrane antigens compared to lymphocytes from control subjects was previously shown to be a marker of cellmediated 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 β-cells (β-CL) was significantly higher in subjects at risk for type 1 diabetes than in age- and sex-matched control blood bank donors (P < 10-6). This number of β-CL was higher in type 1 diabetic patients than in subjects at risk (P < 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 β-CL values (P < 0.001). The percentage of subjects at risk that had a positive test (arbitrarily defined as a β-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 β-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 X2, P = 0.04) and with HLA DR 3/4 heterozygosity (by X2, 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 X2, P < 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 β-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. © 1990 by The Endocrine Society.