Exercise may attenuate faulty gene responsible for high blood sugar: Study
Denmark: One hour of daily exercise is sufficient to help control blood sugar levels in Arctic Inuit with a faulty copy of the TBC1D4 gene, which is responsible for an increased risk of type 2 diabetes (T2D), finds a recent study in Diabetologia.
"We are very excited by the findings, which could improve the lives of many people living with type 2 diabetes in the Arctic region," says Professor Torben Hansen from the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen.
Loss of function of the common muscle-specific TBC1D4 p.Arg684Ter variant defines a subtype of non-autoimmune diabetes in Arctic populations. Homozygous carriers are characterized by elevated levels of postprandial glucose and insulin. It is important to explore possibilities for precision medicine as 3.8% of the Greenlandic population are homozygous carriers.
Against the above background, Torben Hansen and colleagues aimed to investigate whether physical activity attenuates the effect of this variant on 2 h plasma glucose levels after an oral glucose load.
For this purpose, the researchers obtained 2 h plasma glucose levels in a Greenlandic population cohort (n = 2655) after an OGTT, physical activity was estimated as physical activity energy expenditure and TBC1D4 genotype was determined. TBC1D4–physical activity interaction analysis was performed applying a linear mixed model to correct for genetic admixture and relatedness.
Key findings of the study include:
- Physical activity was inversely associated with 2 h plasma glucose levels (β[main effect of physical activity] −0.0033 [mmol/l] / [kJ kg−1 day−1]), and significantly more so among homozygous carriers of the TBC1D4 risk variant compared with heterozygous carriers and non-carriers (β[interaction] −0.015 [mmol/l] / [kJ kg−1 day−1]).
- The estimated effect size suggests that 1 h of vigorous physical activity per day (compared with resting) reduces 2 h plasma glucose levels by an additional ~0.7 mmol/l in homozygous carriers of the risk variant.
"Our finding opens the door to lifestyle precision medicine, in the form of physical activity, that might benefit the 1 in 25 of the Arctic Inuit population who carry two copies of the faulty TBC1D4 gene," says Postdoc Theresia Schnurr from CBMR.
"Physical activity improves glucose homeostasis particularly in homozygous TBC1D4 risk variant carriers via a skeletal muscle TBC1 domain family member 4-independent pathway," concluded the authors. "This provides a rationale to implement physical activity as lifestyle precision medicine in Arctic populations."
The study titled, "Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers," is published in the journal Diabetologia.