Islet beta cell function plays an important role in the pathogenesis of diabetes mellitus, and the destiny of beta cell function failure leads to the uncontrollable hyperglycemia in long term and diabetic complications. From the patients’ point of view, it is of highest priority to find factors for the discrimination of beta cell function course. For autoimmune diabetes, beta cell function failure is more apparent as the immunity mediated beta cell destruction
]. However, the heterogeneous tempo of beta cell function failure in autoimmune diabetes was recognized and LADA is subdivided specially
]. However, the arbitrary classification scheme using onset age to categorize the heterogeneity of autoimmune diabetes has some limitations; 1) the confirmation of the exact onset age is not so certain, 2) the onset age is a continuous parameter, the optimal cut off point is undecided
], 3) the term “latent” in LADA could not be reflected by the “late onset”
], classical type 1 diabetes in adults is common, and “young onset” could also be “latent”.
So, we aimed to investigate whether initial C peptide levels is useful marker for differentiating variation of C peptide decay rate. There were three different outcomes of beta cell function progression, that is, beta cell function failure at the onset of the disease, failure during the follow-up and no failure during the follow-up, and initial fasting C peptide levels was dramatically different in patients with distinct progressive endings of beta cell function. So, we proposed that the disparate outcomes of beta cell function in autoimmune diabetes could be better discriminated by initial FCP levels. When defined beta cell function as B+ or B- by FCP level of 300 pmol/L, we found 13.1% in B+ group while 90.5% in B- group progressed to beta cell function failure. So, initial FCP levels made a better distinction of the heterogeneity in autoimmune diabetes with the sensitivity of 90.5% and specificity of 86.9%.
Positive islet autoantibodies in autoimmune diabetes patients are thought to indicate a progressive autoimmune disease in the beta cells associated with a gradual decrease in insulin secretion. So, islet autoantibodies (A) was applied as one marker to dissect the heterogeneity of ketosis prone diabetes by Maldonado et al., beta cell function (B) was also used, and four different combination of AB groups with diverse clinical features were found. Therefore, the classification scheme using A (autoantibody) and B (beta cell function) was proposed in discriminating ketosis-prone diabetes
For antibody positive autoimmune diabetes, it is likely that the beta cell destruction continues after diagnosis, with varying rate until the beta cells are depleted
]. C-peptide levels at diagnosis, age, gender, titer of GAD-Ab, degree of obesity and puberty, and levels of HbA1c are factors reported to influence beta cell function after diagnosis
]. In our study, we found that initial beta cell function reflected by fasting C peptide levels might be a good marker for dissection the heterogeneity of autoimmune diabetes. The possible reasons are, 1) the value of FCP levels had a higher sensitivity and specificity in predicting beta cell failure; 2) initial C peptide levels could be a mixed reflection of age onset, predisposing genes, the extent of insulin resistance and insulin deficiency. Consistently, Thunander M et al. followed LADA patients for three years, and determined beta-cell function with early insulin vs conventional treatment, and found only baseline level of C-peptide significantly influenced C-peptide level after 3 years
]. Other study reported that initial C-peptide is a predicting factor for effectiveness of insulin intervention for LADA
]. For GAD-Ab positive LADA patients (without classical type 1 diabetes), the same trend of C-peptide declining curve in patients with different initial C-peptide levels, as shown in our Figure
, had been also reported
]. So, the use of initial beta cell function may have important implications in predicting the prognosis of autoimmune diabetes.