Evaluation of residual β-cell function

Posted on October 31, 2009

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A sensitive C-peptide radioimmunoassay was used to assess residual β-cell function (8). We have previously defined a serum C-peptide response (CPR) of <0.033 nmol/l after a 100-g oral glucose load (ΔCPR) as indicating complete β-cell destruction (2,21). To allow more convenient assessment of residual β-cell function over time, a fasting serum C-peptide level below the detection limit (0.017 nmol/l) or a level <0.033 nmol/l at 2–3 h postprandially was also used as a criterion indicating complete β-cell destruction in this study. The time of 2–3 h postprandially was selected because the maximal serum C-peptide level was measured at this point in type 1 diabetic patients undergoing a 100-g oral glucose tolerance test (8). The relationships between these three serum C-peptide criteria for complete β-cell loss were analyzed in 57 of the 266 type 1 diabetic patients.

Assessment of residual β-cell function was done as follows. In 169 patients, the first measurement of serum C-peptide was performed at 5.9 ± 7.9 years (means ± SD) (median 2 years; range 0.08–37 years) after the onset of diabetes, and serum C-peptide was measured a total of 5.1 ± 2.9 times (median 10 times; range 2–14 times) during a disease duration of 13.3 ± 10.5 years (median 10 years; range 0.1–48 years). Complete β-cell loss that occurred among these 169 patients was confirmed by the next measurement of serum C-peptide in all (n = 54) but two patients. In 16 patients, complete β-cell loss was detected by the first assessment of β-cell function performed at 1.1 ± 0.33 years (median 0.45 years; range 0.08–4 years) after the onset of diabetes. In 13 of these 16 patients, complete β-cell loss was confirmed by the next measurement of serum C-peptide. In the four patients who underwent serum C-peptide measurement a total of three times, complete β-cell loss was observed >5 years (median 8 years; range 6–14 years) after the detection of residual β-cell function by the second assessment. Based on the above-mentioned 5-year limit, these patients were censored at the last time when residual β-cell function was detected because time of complete β-cell loss was unknown over the 5-year period. In seven patients, the presence of residual β-cell function was only investigated by one test at 4–24 years (median 14 years) after the onset of diabetes.

Although our study demonstrated the temporal profile of β-cell destruction in type 1 diabetes and detected an HLA allele combination that contributed to early and acute complete β-cell destruction, its retrospective design and one-point determination of serum C-peptide are limitations with respect to delineating longitudinal changes of residual β-cell function. Complete β-cell destruction could have occurred at an earlier time than when it was detected. The potential bias may also be introduced by the exclusion of the patients whose first C-peptide test revealed complete β-cell loss at >5 years after the onset of diabetes from the longitudinal study. Long-term prospective studies on residual β-cell function using the stimulated CPR would be preferable, as suggested by the ADA workshop report (40).

http://diabetes.diabetesjournals.org/content/55/6/1862.full

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