Type 2 diabetes drug can exhaust insulin-producing cells, claims new study

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Long-term use of liraglutide - a drug used to lower blood sugar levels in type 2 diabetes patients - may have a deteriorating effect on insulin-producing beta cells, leading to an increase in blood sugar levels, a new study has claimed.

There is now compelling evidence that liraglutide therapy is efficacious at least in the short term, since it produces an initial reduction in blood sugar. However, many patients do not respond to the treatment and some even display adverse reactions such as nausea, vomiting and diarrhoea.

Researchers from Karolinska Institute in Sweden and University of Miami in US conducted a study on mice implanted with human insulin-producing cells. Blood-sugar suppressors in the form of analogues of the incretin hormone GLP-1 are commonly used in the treatment of type 2 diabetes, since they stimulate the glucose response of the pancreatic beta cells to make them secrete more insulin.

To study the long-term effects of incretin therapy, researchers worked with humanised mice, generated by transplanting human insulin-producing cells into the anterior chamber of the eye. The mice were given daily doses of liraglutide for more than 250 days, during which time the researchers were able to monitor how the pancreatic beta cells were affected.

The results showed an initial improvement in the insulin-producing cells, followed by a gradual exhaustion, with reduced secretion of insulin as a response to glucose. This, they say, was unexpected.

"Given the lack of clinical studies on the long-term effect of these drugs in diabetes patients, this is a very important discovery," said Midhat Abdulreda from University of Miami. "We also need to take these results into account before prescribing blood-sugar suppressing GLP-1 analogues when planning long-term treatment regimens for patients," said Per-Olof Berggren from Karolinska Institute.

"Our study also shows in general how to carry out in vivo studies of the long-term effects of drugs on human insulin-producing cells, which should be extremely important to the drug industry," said Berggren.

The findings were published in the journal Cell Metabolism.

New test to identify infants with rare insulin disease

A rare form of a devastating disease which causes low blood sugar levels in babies and infants may now be recognised earlier, thanks to a new test developed by researchers including one of Indian-origin.

Congenital hyperinsulinism starves a baby's brain of blood sugar and can lead to lifelong brain damage or permanent disability, according to previous research carried out by the University of Manchester team.

The condition occurs when specialised cells in the pancreas release too much insulin which causes frequent low sugar episodes - the clinical opposite of diabetes. Treatment includes drugs to reduce insulin release but in the most serious cases the pancreas is removed.

For some infants with this disease, the release of excess insulin is due to mutations in genes which govern the way our bodies control insulin release.

But for more than two thirds of child patients the genetic causes are not yet known. Genes and hormones were analysed in 13 children with congenital hyperinsulisnism at the Manchester Children's Hospital.

"We have discovered a new clinical test which can identify congenital hyperinsulinism in some patients with no known genetic cause of the disease," said Dr Karen Cosgrove from the Faculty of Life Sciences, who led the research.

"This is the first step to understanding what causes the disease in these particular patients. In future the test may influence how these children are treated medically, perhaps even avoiding the need to have their pancreas removed," said Cosgrove.

The new test measures a pair of hormones called incretins which are released by specialised cells in the gut when food is passing through.

The hormones normally tell the cells in the pancreas to release more insulin to regulate sugar levels in our blood. If the child's body releases too much incretin hormones, the pancreas will release too much insulin causing dangerous low blood sugar levels.

"Although we are the first researchers to report high incretin hormone levels in patients with congenital hyperinsulinism, further studies are needed to see if our test works on a larger group of patients," said Cosgrove.

"Our new results are timely since clinical trials of a new incretin-blocking treatment for congenital hyperinsulinism have recently started. We anticipate that our clinical test will help to identify the patients who are likely to benefit from this new treatment the most," Indi Banerjee, Consultant in Paediatric Endocrinology at Royal Manchester Children's Hospital.

The findings have been published in The Journal of Pediatrics.

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