Diabetes afflicts more than half a billion people worldwide, and causes nearly seven million deaths a year. In recent decades, the prevalence of this disease characterised by elevated levels of blood sugar has skyrocketed around the world.
Now, scientists have made a major breakthrough in developing what has been long called the “holy grail” diabetes treatments — a “smart” insulin that responds in real time to fluctuations in one’s blood sugar level. The research was published in the journal Nature on Wednesday.
Diabetes & treatment
There are two kinds of diabetes. Both are related to the body’s ability to synthesise and react to insulin, the hormone that breaks down sugar in the blood to produce energy.
Type 1 diabetes, which often starts in childhood, occurs when the pancreas do not produce insulin (or enough insulin). Type 2 diabetes sees the cells of the body develop resistance to insulin, meaning greater amounts are reequired that what is produced by the pancreas.
Both conditions are managed by the administration of synthetic insulin. But this poses a fundamental challenge as the blood glucose levels in the body are not constant. Blood glucose levels falling too much due to the overdosage insulin in the body can be life-threatening. Most patients have to constantly monitor their insulin levels, and adjust doses accordingly.
For decades, scientists have thus tried to develop glucose-sensitive insulin therapies. Thus far, the most advanced glucose-sensitive systems rely on the molecule being stored somewhere in the body (like in a packet under the skin), and being released based on one’s blood sugar level, which is detected by a sensor attached to the body.
Engineering insulin
For the latest study, however, an international team of scientists from companies in Denmark, the UK, and Czechia, as well as the University of Britol, have modified the insulin molecule itself to give it an “on-and-off switch” that automatically responds to changing blood glucose levels.
The newly developed insulin named NNC2215 comprises two parts: a ring-shaped structure, and a molecule with a similar shape to glucose called a glucoside. When blood sugar levels are low, the glucoside binds to the ring, keeping the insulin in an inactive state to prevent further lowering of blood sugar. But, as blood glucose rises, the glucoside is replaced by glucose itself, triggering the insulin to shift its shape and become active, helping bring blood sugar levels down to safer ranges.
Reacting to the research, Dr Elizabeth Robertson, Director of Research at Diabetes UK, said: “The hope is that this will ease the constant challenge of managing blood sugar highs and lows, and improve the physical and mental health of millions of people worldwide with diabetes who rely on insulin therapy.”
Researchers who developed NNC2215 found it to be as effective as human insulin at lowering blood glucose in rats and pigs. Human trials will be conducted in the near future.
At the moment, the major problem with NNC2215 is that its activation and impact are not gradual. The engineered insulin requires a significant glucose spike to be activated, and once it is activated, there is a sudden rush of insulin in the system. Scientists are currently working to refine the molecule so that it is activated gradually, and insulin levels rise more slowly.
