A genetic variant specifically found in people from Greenland can trigger the development of type 2 diabetes, latest research has highlighted.
Researchers from the University of Copenhagen have found that 4% of the Greenlandic Inuit population carry a specific mutation in the TBC1D4 gene, increasing their risk of type 2 diabetes by tenfold.
Current medications are unable to prevent the development of the condition among these affected individuals, the study has reported.
However, physical activity has the potential to combat the development of type 2 diabetes among those carrying the genetic variant, according to the researchers.
The current number of type 2 diabetes cases in Greenland is almost 50% higher than in Denmark, data has shown.
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First author Professor Jørgen Wojtaszewski said: “These 4% carry a specific mutation in the TBC1D4 gene, which gives them a tenfold increased risk of type 2 diabetes.
“The gene variant makes them highly glucose intolerant – meaning that when they consume sugar, they struggle to get it out of their bloodstream.”
He added: “We can see that people with this genetic variant have insulin-resistant musculature. This means that their muscle tissue responds poorly to insulin, which is critical, as muscles account for the majority of the body’s sugar uptake. Consequently, this condition dramatically increases their risk of developing type 2 diabetes.
“What’s particularly unique is that insulin resistance is typically present not just in muscles, but in the liver, fat tissue, and other organs and cells as well. But for carriers of this gene variant, resistance is found only in the muscles, which is unprecedented.”
As long as their pancreas can effectively release insulin, people carrying the genetic variant do not become ill and their other organs maintain normal insulin sensitivity.
Professor Jørgen Wojtaszewski noted: “Unlike other pre-diabetic conditions, these individuals do not exhibit elevated fasting blood sugar or insulin levels, nor indicators of heightened long-term blood sugar. And this makes it all the more challenging for doctors to detect.
“It turns out that even a single training session involving one hour of moderate physical activity increases insulin sensitivity in the muscles of gene variant carriers – although the effect is not as pronounced as in non-carriers.”
He continued: “This strongly suggests that muscle use through physical activity can reduce the risk of type 2 diabetes in gene variant carriers.
“People with this gene variant have constituted a relatively large part of the population for hundreds of years, and they will continue to for generations to come. Now we can advise them on how to prevent diabetes — namely through physical activity.”
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He added: “The challenge with treating carriers using conventional diabetes medications is that these drugs do not increase insulin sensitivity in muscle but primarily serve to reduce sugar production in the liver, which subsequently lower overall blood sugar levels.
“However, since carriers of the variant do not have elevated blood sugar levels when not eating, such treatment carries a significant risk of causing dangerously low blood sugar.”
He concluded: “We know that a particular enzyme, one activated during physical activity, positively influences TBC1D4 activity.
“The pharmaceutical industry is already working to identify molecules that can activate this enzyme to regulate TBC1D4 activity, and in doing so, enhance insulin sensitivity. If such a drug reaches the market, it could benefit most other forms of type 2 diabetes.”
Read the full study in the journal Nature Metabolism.
