Homogeneity in Pattern of Decline of β-Cell Function in IDDM: Prospective study of 204 consecutive cases followed for 7.4 yr

Abstract

OBJECTIVE To study the natural history of β-cell function from onset of IDDM to expected deterioration of insulin (C-peptide) secretion and to identify different patterns of decline, if any. RESEARCH DESIGN AND METHODS A cohort of 204 consecutive newly diagnosed IDDM (clinical criteria) patients were followed prospectively for 7.4 yr (range 6–9 yr), measuring fasting C-peptide at onset, 1, 3, 6, 9, 12, and then every 6 mo until 106 wk (range 104–135 wk). Then, postprandial C-peptide was measured. RESULTS Fasting C-peptide was 0.17 nM (range 0.11–0.25 nM) at onset followed by an annual increase rate of 0.16 nM/yr (range 0.06–0.48 nM/yr) to a peak of 0.28 nM (range 0.23–0.34 nM/yr) after 25 wk (range 12–39 wk). The subsequent annual decline rate of fasting C-peptide was 0.08 (0.05–0.12) and of postprandial C-peptide 0.03 nM/yr (range 0.02–0.06 nM/yr). None of these parameters showed bimodality in their distribution. However, some parameters were important. In men, fasting C-peptide at onset was lower, but the initial C-peptide increase rate was more pronounced compared to women. Furthermore, insulin-free remission was related to higher C-peptide levels throughout the study. C-peptide was higher during the 1st yr of diabetes in subjects > 30 yr of age at onset compared with younger diabetic patients. Stepwise multiple regression analysis showed that age, male sex, and fasting C-peptide at onset were of some predictive value for the C-peptide levels at 5 yr. However, simple group comparisons revealed no significant differences. CONCLUSIONS No major heterogeneity exists in the pattern of decline of β-cell function in IDDM, although small differences in pattern could be identified in both sexes, in different age-groups, and in relation to achieving insulin-free remission.