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Clin Chem. 2018 Aug;64(8):1203-1210. doi: 10.1373/clinchem.2017.285841. Epub 2018 Jun 26.

Dietary Intakes and Circulating Concentrations of Branched-Chain Amino Acids in Relation to Incident Type 2 Diabetes Risk Among High-Risk Women with a History of Gestational Diabetes Mellitus.

Author information

1
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
2
Broad Institute of MIT and Harvard, Cambridge, MA.
3
Center for Lipid Metabolomics and Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
4
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
5
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA.
6
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
7
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
8
Mary Horrigan Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
9
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. zhangcu@mail.nih.gov.

Abstract

BACKGROUND:

Circulating branched-chain amino acids (BCAAs; isoleucine, leucine, valine) are consistently associated with increased type 2 diabetes (T2D) risk, but the relationship with dietary intake of BCAAs is less clear.

METHODS:

The longitudinal Nurses' Health Study II cohort conducted a blood collection from 1996 to 1999. We profiled plasma metabolites among 172 incident T2D cases and 175 age-matched controls from women reporting a history of gestational diabetes before blood draw. We estimated dietary energy-adjusted BCAAs from food frequency questionnaires. We used conditional logistic regression models to estimate odds ratios (OR) and 95% CI of T2D risk across quartiles (Q1-Q4) of BCAAs, adjusting for age, body mass index (BMI), physical activity, family history, and other established risk factors. We also assessed joint exposure to below/above medians of diet and plasma concentrations, with lower diet/lower plasma as reference.

RESULTS:

Dietary and plasma BCAA concentrations were positively associated with incident T2D (diet Q4 vs Q1 OR = 4.6, CI = 1.6, 13.4; plasma Q4 vs Q1 OR = 4.4, CI = 1.4, 13.4). Modeling the joint association indicated that higher diet BCAAs were associated with T2D when plasma concentrations were also higher (OR = 6.0, CI = 2.1, 17.2) but not when concentrations were lower (OR = 1.6, CI = 0.61, 4.1). Conversely, higher plasma BCAAs were associated with increased T2D for either lower or higher diet.

CONCLUSIONS:

Independent of BMI and other risk factors, higher diet and plasma BCAA concentrations were associated with an increased incident T2D risk among high-risk women with a history of gestational diabetes, supporting impaired BCAA metabolism as conferring T2D risk.

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