Beta-cell loss most rapid when diabetes diagnosed very young
By Eleanor McDermid, medwireNews Reporter
Children who are diagnosed with type 1 diabetes in early childhood have the most rapid loss of beta cells, research shows.
“Our results add weight to the proposal that intervention trials should be powered separately for each age at diagnosis group and highlight that consideration of age at diagnosis is very important in the interpretation of outcomes”, write Alice Carr (University of Exeter Medical School, UK) and study co-authors in Diabetes.
The team’s findings also show a close association between plasma C-peptide levels in living children with diabetes and beta-cell loss in pancreatic samples from deceased donors with diabetes, supporting C-peptide as “a reliable, inexpensive and practical marker” of beta-cell loss in diabetes.
The researchers used non-fasting C-peptide samples from 4079 participants of the UK Genetic Resource Investigating Diabetes cohort who were diagnosed with type 1 diabetes at the age of 16 years or younger. They also studied 235 pancreatic samples from the network for Pancreatic Organ donors with Diabetes (nPOD) biobank and the Exeter Archival Diabetes Biobank, all belonging to people diagnosed with diabetes when younger than 18 years.
During the first year after diagnosis, the majority of children had detectable C-peptide, irrespective of their diagnosis age, at 90% of those diagnosed younger than 7 years, 97% of those diagnosed aged 7–12 years and 95% of those diagnosed at the age of 13 years or older.
But at 1–5 years after diagnosis, the proportion of children with detectable C-peptide declined sharply, particularly in the youngest age groups, with corresponding rates of 33%, 61% and 78%.
The same pattern was observed in donor pancreatic samples, with insulin-positive beta cells detectable within the first year after diabetes diagnosis in 88%, 97% and 88% of children diagnosed when younger than 7 years, 7–12 years and 13 years or older, respectively.
But the corresponding rates at 1–5 years after diagnosis were 8%, 54% and 88%.
In addition, the median C-peptide level in children in whom it could be detected during the first year after diagnosis was significantly lower in those diagnosed when younger than 7 years versus 13 years or older, at 61.5 versus 199.5 pmol/L.
Again this was reflected in the pancreatic samples, in which the median beta-cell area was 15% in the youngest age group compared with 31% in the oldest children. The researchers note that the median beta-cell area in young donors (median age=9 years) without diabetes was 70.4%.
Nevertheless, a small proportion of children with diabetes did still have detectable C-peptide levels and insulin-positive beta cells 10 years or more after diagnosis, even those diagnosed when very young.
The researchers say their findings indicate that “progressive loss of β-cells is the main contributory factor to the decline in endogenous insulin secretion observed in children and young people diagnosed with type 1 diabetes.”
And they add that the “rapid depletion” of beta cells in the youngest children during the first year after diagnosis “emphasizes that early intervention close to (or before) diagnosis may be most time critical in those progressing to disease in very early life.”
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Diabetes 2022; doi:10.2337/db22-0097