Clinical evolution of beta cell function in youth with diabetes: the SEARCH for Diabetes in Youth study
OBJECTIVE To study the natural history of beta-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 greater than 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 beta-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.