Markers of progression to type 1 diabetes proposed
medwireNews: Changes in the gut microbiome, microRNAs, glucose response curves, and pancreas volume may all be associated with progression to type 1 diabetes, reported researchers at the ADA’s 78th Scientific Sessions in Orlando, Florida, USA.
Jenny Couper, from the University of Adelaide in South Australia, showed that children (aged 5–20 years) with multiple islet autoimmunity (n=18) or recent-onset type 1 diabetes (n=29) had a microbial imbalance (dysbiosis) in the gut, which presented as a significantly lower proportion of anti-inflammatory bacteria, such as Buytyricimonas paravirosa and Prevotell sp. compared with controls (n=41) matched for age and sex.
Children who progressed to type 1 diabetes also had higher small intestinal permeability than nonprogressors and this correlated with lower gut microbiome richness and lower plasma acetate.
Couper concluded that the findings could help to “inform bespoke probiotic development” and may also provide data “supporting a mechanism for progression to type 1 diabetes.”
Mugdha Joglekar, from the University of Sydney in New South Wales, Australia, described how her team developed a microRNA signature for type 1 diabetes that ultimately included 50 microRNAs that were associated with insulin expression during embryonic development, were predictive of and necessary for insulin transcription, and were dysregulated in individuals with type 1 diabetes.
When Joglekar and team profiled samples from 921 ethnically diverse individuals, they found that 31 microRNAs were important for stratifying patients with and without type 1 diabetes, 18 of which were common to all three populations studied (Australian, Hong Kong Chinese, and Indian).
She said that further studies are now looking at the value of microRNAs in high-risk individuals and whether there are any correlations with covariates such as glycated hemoglobin and diabetes duration.
Glucose response curves (GRC) may also help predict which patients will progress to type 1 diabetes, according to Heba Ismail (Children’s Hospital of Pittsburgh of UPMC in Pennsylvania, USA).
She reported that progressors (n=360) were a significant three times more likely to change from having a biphasic GRC at baseline to having a monophasic curve on their last oral glucose tolerance test before diabetes diagnosis than nonprogressors (n=2404).
They were also a significant 8.9 times more likely to progress from a monophasic to monotonic curve.
Furthermore, the change from biphasic to monophasic GRCs in progressors and from monophasic to monotonic in both progressors and nonprogressors corresponded to a decline in β-cell function as indicated by the early C-peptide response.
Ismail concluded that GRC changes “add to the markers of risk for progression.”
Jack Virostko, from the University of Texas at Austin, USA, and colleagues used longitudinal magnetic resonance imaging (MRI) of the pancreas in 51 individuals with recent-onset type 1 diabetes (mean age 13.7 years) to show that these patients have a pancreas volume that is approximately 30% smaller than that of age-matched controls (n=51).
He also showed that pancreas volume decreased by 0.8% per month during the year following diabetes diagnosis, whereas in controls it increased by 0.9% per month during the same period, a difference that was statistically significant.
In the 16 individuals with multiple islet autoantibodies pancreas volume was between that of controls and people with type 1 diabetes, he added.
Virostko concluded that the data suggest “existence of ongoing pancreatic atrophy during the first year after diagnosis with [type 1 diabetes] which may be reflected by microstructural changes in the pancreas.”
By Laura Cowen
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