Newswise—A novel study in AACC’s Clinical Chemistry journal shows that women with a history of gestational diabetes are at increased risk for type 2 diabetes if they eat a diet high in branched-chain amino acids (BCAAs) and can’t metabolize BCAAs effectively. This research could improve diabetes prevention strategies by enabling better identification and more targeted care of women at high risk for this condition.

Prevention efforts focused on groups at high risk for type 2 diabetes are needed to curb the global epidemic of this condition, and women with a history of gestational diabetes are a key high-risk group to target. Gestational diabetes affects 2%-10% of pregnancies in the US every year, and although symptoms often disappear within weeks of giving birth, 50% of women who have had gestational diabetes will go on to develop type 2 diabetes in their lifetimes. High blood levels of BCAAs, which come from both animal and vegetable sources of protein, are associated with increased type 2 diabetes risk in the general population, and could help to pinpoint women with a gestational diabetes history who need to make health care or lifestyle changes to prevent type 2 diabetes development. No previous studies, however, have investigated the link between BCAAs and diabetes onset in this population.

A team of researchers led by Cuilin Zhang, MD, PhD, MPH, of the National Institutes of Health in Bethesda, Maryland, has now shown that, among women in this population, those with both high BCAA blood levels and dietary intake are at a striking 4- to 6-fold increased risk for type 2 diabetes. To determine this, the researchers measured blood concentrations of the BCAAs isoleucine, leucine, and valine in 347 women with a history of gestational diabetes, 172 of whom had developed type 2 diabetes and 175 of whom had not. The researchers also estimated dietary intake of these three BCAAs in all subjects using questionnaires. Zhang’s team then statistically analyzed the data from the blood measurements and questionnaires while adjusting for age, BMI, physical activity, family history, and other established risk factors for type 2 diabetes.

Notably, from this, Zhang’s team also discovered that high dietary BCAAs were only associated with type 2 diabetes when blood levels were also high, but not when blood levels were low. Conversely, high BCAA blood levels were associated with increased type 2 diabetes risk regardless of dietary levels. This indicates that preventive strategies aimed at improving BCAA metabolism, such as weight loss and aerobic exercise, might result in the greatest reduction of type 2 diabetes risk in women with a history of gestational diabetes.

“Uncovering dietary and/or plasma BCAA’s role in [type 2 diabetes] pathophysiology may help to develop targeted therapies and identify high-risk individuals,” said Zhang. “Follow-up studies are warranted to determine whether interventions, including lifestyle modifications, lead to reductions in isoleucine, leucine, or valine metabolite levels and subsequently reduced [type 2 diabetes] risk.”