medwireNews: Beta-cell function enters a period of rapid decline around 6 months before people meet the diagnostic threshold for type 1 diabetes, show TrialNet data.
The researchers identified a period of rapidly declining beta-cell function, following a period of relatively stable function. But the study participants did not meet the ADA criteria for diagnosis (fasting glucose ≥126 mg/mL or 2-hour glucose ≥200 mg/dL) until they were approximately 6 months into this period of rapid decline.
“Importantly, these data highlight the discordant timing between accelerated β-cell dysfunction and the current glucose thresholds for diagnosis,” Magdalena Bogun (Columbia University, New York, USA) and study co-authors write in Diabetes Care.
“To preserve β-cell function, disease-modifying therapy should start at or before the acute decline.”
The 80 study participants were first- or second-degree relatives of people with type 1 diabetes who were themselves diagnosed with the condition while being monitored with 6-monthly oral glucose tolerance tests (OGTTs) as part of the TrialNet Pathway to Prevention Protocol.
The research team identified “subtle changes” in C-peptide levels starting from around 12 months before diagnosis, but the significant fall in beta-cell function began approximately 6 months before diagnosis and continued until around 12 months after, at a consistent rate of decline across the whole period.
“Ironically, the knowledge that autoimmunity begins long before diagnosis has directed the search for disease triggers in early life, and these data highlight the gap in knowledge about how external insults alter disease course after (often long after) autoimmunity is present,” the team observes.
The study participants comprised 20 who were younger than 11 years, 35 aged between 11 and 20 years, and 25 who were older. Age affected the rate of C-peptide change, with older people having a less precipitous rate of decline than the younger participants, but all age groups followed the same pattern and timing of decline in beta-cell function.
Change in glucose levels generally matched that for C-peptide. But whereas 2-hour glucose began to change around 12 months before diagnosis, in line with the earliest changes in C-peptide, fasting glucose did not start to rise until 6 months beforehand.
“Thus, our study pinpoints a window from ~6 months on either side of clinical diagnosis in which rapid changes in β-cell function are occurring,” conclude Bogun and colleagues.
They add: “Data presented here suggest that the window for effective immunotherapy starts 6–12 months before the clinical diagnosis.”
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