Cumulative consumption of branched-chain amino acids and incidence of type 2 diabetes

Background: Plasma branched-chain amino acids (BCAAs, including leucine, isoleucine and valine) were recently related to risk of type 2 diabetes (T2D). Dietary intake is the only source of BCAAs; however, little is known about whether habitual dietary intake of BCAAs affects risk of T2D. Methods: We assessed associations between cumulative consumption of BCAAs and risk of T2D among participants from three prospective cohorts: the Nurses' Health Study (NHS; followed from 1980 to 2012); NHS II (followed from 1991 to 2011); and the Health Professionals Follow-up Study (HPFS; followed from 1986 to 2010). Results: We documented 16 097 incident T2D events during up to 32 years of follow-up. After adjustment for demographics and traditional risk factors, higher total BCAA intake was associated with an increased risk of T2D in men and women. In the meta-analysis of all cohorts, comparing participants in the highest quintile with those in the lowest quintile of intake, hazard ratios (95% confidence intervals) were for leucine 1.13 (1.07-1.19), for isoleucine 1.13 (1.07-1.19) and for valine 1.11 (1.05-1.17) (all P for trend < 0.001). In a healthy subsample, higher dietary BCAAs were significantly associated with higher plasma levels of these amino acids (P for trend = 0.01). Conclusions: Our data suggest that high consumption of BCAAs is associated with an increased risk of T2D.