Meal-stimulated C-peptide and insulin antibodies in type I diabetic subjects and their nondiabetic siblings characterized by HLA-DR antigens.

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 greater than or equal to 1.8 ng/ml were seen significantly less often in patients who were less than 10 yr old at the time of diagnosis of IDDM than in patients who were greater than 10 yr old at the time of diagnosis (8% versus 21%, P less than 0.05). More patients with HLA-DR4 had a CP response greater than or equal to 1.8 ng/ml than did patients who lacked this antigen whether duration of IDDM was less than 10 yr (30% versus 18%, P greater than 0.05) or greater than or equal to 10 yr (15% versus 0%, P less than 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 less than 10 yr (1.7 +/- 1.9 versus 1.4 +/- 1.0, P less than 0.01) and greater than or equal to 10 yr (1.2 +/- 1.5 versus 1.0 +/- 0.4, P less than 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 less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)