Affiliation:
1. University of Minnesota School of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, and the University of Minnesota General Clinical Research Center
Abstract
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.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
15 articles.
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