RESIDUAL BETA-CELL FUNCTION AND HLA-A24 IN IDDM - MARKERS OF GLYCEMIC CONTROL AND SUBSEQUENT DEVELOPMENT OF DIABETIC-RETINOPATHY

To identify risk factors for diabetic retinopathy in insulin-dependent diabetes mellitus (IDDM), we studied the relationships among residual beta-cell function, human leukocyte antigen (HLA), long-term glycemic control, and development of diabetic retinopathy in 128 IDDM patients, Residual beta-cell function was assessed by serum C-peptide immunoreactivity (CPR) response to a 100-g oral glucose load (Delta CPR). The patients were stratified into three groups: those with Delta CPR of <0.033 nmol/l (group 1, n = 50), those with Delta CPR of 0.033-0.1 nmol/l (group 2, n = 38), and those with Delta CPR of >0.1 nmol/l (group 3, n = 40), The cumulative incidence rate of background retinopathy was higher in the order of groups 1, 2, and 3 (P = 0,032), Group 1 progressed to preproliferative retinopathy at an earlier stage than did groups 2 and 3 combined (P = 0.028), Further progression to proliferative retinopathy tended to be earlier in group 1 than in groups 2 and 3 combined (P = 0.083), The mean HbA(1c) value rose from 9.01 +/- 1.06% (mean +/- SD) in group 3 to 9.75 +/- 0.79% in group 2 to 10.48 +/- 1.12% in group 1 (P < 0.0001), In group 1, 89.6% of the patients had HLA-A24, whereas 50 and 43.6% of the patients had this antigen in groups 2 and 3 respectively (P < 0.0001), in Cox's proportional hazards model, both serum CPR response and mean HbA(1c) value were identified as independent risk factors for development of diabetic retinopathy after adjusting for other potential risk factors, These results indicate that complete loss of beta-cell function, which is associated with HLA-A24, predicts earlier occurrence of diabetic retinopathy through metabolic control.