Why is it that, despite consuming the same number of calories, sodium and sugar, some people face little risk of diabetes or obesity while others are at higher risk? A new study by investigators at Brigham and Women’s Hospital has uncovered mutations in a gene that appear to help drive this difference. Individuals with a specific variant in a gene known as SGLT1, which results in reduced uptake of sugars in the gut, had lower incidence of obesity, diabetes, death and heart failure, suggesting that SGLT1 may make a promising therapeutic target for metabolic disease. The team’s results were recently published in the Journal of the American College of Cardiology.
“These SGLT1 mutations have not been characterized in the general population before,” said first author Sara Seidelmann, MD, PhD, who performed this work as a clinical and research fellow in the Division of Cardiovascular Medicine at the Brigham working with senior author Scott Solomon, MD, professor of Medicine and The Edward D. Frohlich distinguished chair at the Brigham. “We were able to evaluate the association of genetic mutations in SGLT1 with the rise in blood sugar that occurs in response to dietary glucose in several large populations.”
Carbohydrates that enter the body are broken down in the small intestine into smaller pieces, such as glucose, and absorbed into bodily tissues. The sodium/glucose co-transporter-1 (SGLT1) protein plays a critical role in glucose transport into these tissues. Another SGLT family member – SGLT2 – is the target of a class of diabetes drugs known as SGLT2 inhibitors. Researchers believe that while SGLT2 inhibitors stop glucose re-uptake in the kidneys, inhibiting SGLT1 could reduce glucose uptake at the source – the small intestine – which might reduce the carbohydrate load after a large meal.