We studied serum C-peptide (CP) response 90 min after a breakfast meal and insulin antibody titers in 171 type I diabetic (IDDM) patients and 272 of their nondiabetic siblings from 169 unrelated families. HLA typing was performed in all participants.
In IDDM patients, there was a decline in CP response with increased duration of disease. CP responses of >1.8 ng/ml were seen significantly less often in patients who were <10 yr old at the time of diagnosis of IDDM than in patients who were >10 yr old at the time of diagnosis (8% versus 21%, P < 0.05). More patients with HLA-DR4 had a CP response >1.8 ng/ml than did patients who lacked this antigen whether duration of IDDM was <10 yr (30% versus 18%, P > 0.05) or >10 yr (15% versus 0%, P < 0.05). Mean C-peptide was also higher in HLA-DR4-positive patients compared with HLA-DR4-negative patients both when duration of disease was <10 yr (1.7 ±1.9 versus 1.4 ± 1.0, P < 0.01) and >10 yr (1.2 ± 1.5 versus 1.0 ± 0.4, P < 0.0001). Insulin antibody binding was slightly higher in patients with HLA-DR4 compared with patients lacking this antigen (5.96 ± 7.20 versus 4.89 ± 4.74, P < 0.001).
The nondiabetic male sibs had higher postprandial plasma glucose (PG) (84 ± 22 versus 79 ± 20, P < 0.05) and lower serum CP values (3.8 ±1.6 versus 4.2 ± 1.7, P < 0.05) than did female sibs. There were no differences in mean PG or CP values in sib groups characterized by HLA-DR type or HLA haploidentity with IDDM probands.
In conclusion, pathogenetic heterogeneity of IDDM is supported here by the following: (1) patients with earlier onset of IDDM seem to have more severe beta cell insult, and (2) DR4-positive patients give evidence of better preservation of beta cell function, even in the earlier onset classes.