Scientists ID new way to help predict, track CF-related diabetes
Blood markers could flag early CFRD in adults, research suggests
Written by |
Levels in the bloodstream of certain circulating microRNAs — small strands of genetic material that help regulate gene activity — may flag changes linked to cystic fibrosis-related diabetes (CFRD), or its development, in people with cystic fibrosis (CF).
That’s according to a new study by researchers in Europe who sought to identify blood markers that could predict the risk of this CF complication among patients, and track the condition when it occurs.
The researchers found that two microRNAs, miR-34a-5p and miR-122-5p, are seen at higher blood levels in people with early problems controlling blood sugar and in those with CFRD. That suggests that they may be promising blood-based biomarkers that could be used in tracking the condition.
In contrast, higher levels of a third microRNA, miR-223-3p, were linked to better blood sugar control in people without diabetes — a relationship not seen in those with impaired glucose control or CFRD. That finding suggests this microRNA may play a role in the disease’s development, which could potentially make it a marker of diabetes risk in people with CF.
“This hypothesis-generating study can serve as a solid platform for future investigations into the potential role for circulating microRNAs as diagnostic, monitoring and predictive biomarkers in CFRD, ” the researchers wrote, adding, “We propose that circulating microRNAs can serve as biomarkers for CF complications.”
The study, “Dynamic changes in circulating microRNAs during oral glucose tolerance testing support their potential as diagnostic and monitoring biomarkers in cystic fibrosis-related diabetes,” was published in the journal Diabetologia.
CFRD, a common complication of CF affecting at least half of adults with the disease, is characterized by elevated blood glucose, or sugar, levels. This mainly happens because insulin-producing cells in the pancreas, called beta cells, stop working properly over time. Insulin is the hormone that allows blood glucose to enter cells and be used for energy. When too little insulin is released, blood glucose levels rise.
MicroRNAs in blood may indicate disease progression
MicroRNAs circulating in the bloodstream may act as indicators of disease status or progression and may also help different organs communicate with one another.
For example, studies show that microRNAs released from fat tissue can affect how the liver regulates blood sugar. Meanwhile, microRNAs from immune cells can enter beta cells and influence insulin production and cell survival.
Based on this knowledge, the researchers hypothesized that circulating microRNA patterns may differ depending on glucose tolerance — a measure of how well the body clears sugar from the blood after consuming it — in people with CF. The team also theorized that some microRNAs may change quickly when blood glucose levels rise.
To investigate this, researchers in Denmark, Sweden, and the U.K. analyzed blood microRNA levels in 93 adults with CF who underwent an oral glucose tolerance test (OGTT). The OGTT measures the body’s immediate response to sugar. Participants consumed a sugary drink; blood sugar levels were measured before drinking and at 10 minutes, 30 minutes, one hour, and three hours afterward.
Based on glucose tolerance, participants were classified into four groups: normal glucose tolerance, where blood sugar stays in the normal range throughout the test; indeterminate glucose tolerance, where blood sugar briefly spikes but is normal at two hours; impaired glucose tolerance, where blood sugar remains higher than normal at two hours; and CFRD, where two-hour blood sugar levels meet the criteria for diabetes.
To identify microRNAs of interest, the researchers first analyzed samples from a smaller subgroup of 12 participants — three from each group. Among 275 microRNAs consistently detected in these samples, 16 showed distinct patterns either before glucose intake or in response to the glucose drink. These were then examined in the full study group, where eight were confirmed to differ by glucose tolerance status or in their responses during the test.
Among these, the researchers highlighted three — miR-34a-5p, miR-122-5p, and miR-223-3p — for their potential as blood-based biomarkers of CFRD or for their involvement in the development of diabetes in people with CF.
Higher levels linked to markers of liver damage in CFRD
Higher blood levels of two — miR-34a-5p and miR-122-5p — were seen at baseline, or the study’s start, in people with indeterminate glucose tolerance and in those with CFRD. In people with CFRD, higher blood levels of these microRNAs were also associated with higher levels of certain liver enzymes commonly used as markers of liver damage.
Because blood levels of miR-122-5p are elevated in CF-related liver disease, high levels of this microRNA may “be indicative of both CFRD development and liver damage,” the researchers wrote. In contrast, the role of miR-34a-5p was less clear, as this microRNA is produced in several major organs.
MiR-223-3p showed a different pattern. Its baseline blood levels were similar across groups, but it rose 30 minutes after glucose intake in people with impaired glucose tolerance. In people with normal glucose tolerance, higher miR-223-3p levels were linked to lower blood sugar levels at 30 and 60 minutes during the test and to higher insulin levels at baseline.
These findings suggest that miR-223-3p may help the body respond to rising blood sugar by supporting insulin release. But in people with more advanced problems controlling blood sugar, including those with CFRD, this link was no longer seen, suggesting the system may stop working properly as the disease progresses.
Finally, experiments using insulin-producing cells grown in the laboratory showed that increasing levels of miR-122-5p boosted insulin release in response to glucose by about 60%. Higher levels of miR-223-3p boosted it by 45%. This would be beneficial in CFRD, the researchers noted.
In contrast, higher levels of miR-34a-5p reduced the survival of these cells, suggesting it may contribute to damage of insulin-producing cells.
“MiR-34a-5p and miR-122-5p show potential as biomarkers for CFRD development and liver damage,” the researchers concluded. “MiR-122-5p and miR-223-3p could mitigate CFRD development by increasing the secretory capacity of the beta cells while miR-34a-5p might propagate CFRD development by reducing cell viability.”
