Treating patients with a rare, genetic form of diabetes with therapies aimed at type 2 diabetes could be harmful, and there needs to be a review of treatment guidelines for such cases.
This was the conclusion researchers from Washington University School of Medicine in St. Louis, MO, came to in a study published in The Journal of Biological Chemistry.
Maturity-onset diabetes of the young (MODY1) is a rare, genetic form of diabetes that is often misdiagnosed as type 2 diabetes because the two forms share similar symptoms. MODY1 accounts for 3-5% of all patients with diabetes.
However, the researchers suggest the underlying mechanisms of MODY1 are very different to type 2 diabetes, and treating it with drugs for type 2 diabetes appears to kill insulin-secreting beta cells, causing patients to move onto insulin injections much sooner.
Within 10 years of diagnosis, many MODY1 patients find themselves having to inject with insulin as a way to keep their blood sugar under control.
First author Dr. Benjamin D. Moore, formerly of Washington University and now at Massachusetts General Hospital, explains that drugs for type 2 diabetes make insulin-secreting beta cells very active, and adds:
“But the MODY1 pathway we’ve uncovered shows that stimulating those cells with those drugs can lead to beta cell death. That means these patients can become dependent on insulin injections much sooner.”
The researchers found that boosting beta cell activity with medication kills them off by increasing cell stress and, instead, patients with MODY1 may benefit from other types of medication that target a specific pathway that is important for the cells.
They came to this idea after discovering patients with MODY1 have a gene mutation that affects a protein that controls a component in cells that produce insulin and enzymes in the stomach, liver, kidney and intestines.
The protein is called XBP1, and it controls the development and maintenance of the endoplasmic reticulum (ER) – a labyrinth-like, tubular cell component that, among other things, synthesizes lipids, proteins and many other building blocks of glucose metabolism.
Initially, the researchers were studying cells in the stomach when they came across the pathway. They suggest the discovery may also have implications for disorders involving cells that secrete other enzymes.
Senior author Jason Mills, an associate professor of medicine at Washington University, explains that while the cells themselves may be quite different, their enzyme-making machinery – such as their ER – is very similar. He likens this to car manufacturing, where, while different models of cars may look quite different, the layout and equipment in the auto plant are not. He adds:
“It appears the same thing may be true for a number of these cells that secrete key enzymes in the gastrointestinal tract.”
Prof. Mills and his team are continuing to investigate whether the same pathways are active in different types of cell that secrete enzymes.
In the meantime, the researchers suggest doctors treating diabetes patients should establish whether they have the MODY1 form before deciding on treatments, as Dr. Moore notes:
“It’s important to diagnose patients as accurately as possible and to attempt to target the correct pathway.”
The study follows another that Medical News Today learned about in June 2015, where, thanks to a new drug screening tool, scientists discovered a new compound that acts on an endoplasmic reticulum pathway to potentially target the cause of type 2 diabetes.