Tabák, A.G. et al. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet 373, 2215–2221 (2009).
Wilson, P.W. et al. Prediction of incident diabetes mellitus in middle-aged adults: the Framingham Offspring Study. Arch. Intern. Med. 167, 1068–1074 (2007).
Pan, X.R. et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 20, 537–544 (1997).
Tuomilehto, J. et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N. Engl. J. Med. 344, 1343–1350 (2001).
The Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 346, 393–403 (2002).
Gerstein, H.C. et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 368, 1096–1105 (2006).
Nicholson, J.K. & Wilson, I.D. Opinion: understanding 'global' systems biology: metabonomics and the continuum of metabolism. Nat. Rev. Drug Discov. 2, 668–676 (2003).
Raamsdonk, L.M. et al. A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations. Nat. Biotechnol. 19, 45–50 (2001).
Allen, J. et al. High-throughput classification of yeast mutants for functional genomics using metabolic footprinting. Nat. Biotechnol. 21, 692–696 (2003).
An, J. et al. Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance. Nat. Med. 10, 268–274 (2004).
Sabatine, M.S. et al. Metabolomic identification of novel biomarkers of myocardial ischemia. Circulation 112, 3868–3875 (2005).
Sapieha, P. et al. The succinate receptor GPR91 in neurons has a major role in retinal angiogenesis. Nat. Med. 14, 1067–1076 (2008).
He, W. et al. Citric acid cycle intermediates as ligands for orphan G-protein–coupled receptors. Nature 429, 188–193 (2004).
Newgard, C.B. et al. A branched-chain amino acid–related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 9, 311–326 (2009).
Shaham, O. et al. Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity. Mol. Syst. Biol. 4, 214 (2008).
Wopereis, S. et al. Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes. PLoS ONE 4, e4525 (2009).
Zhao, X. et al. Changes of the plasma metabolome during an oral glucose tolerance test: is there more than glucose to look at? Am. J. Physiol. Endocrinol. Metab. 296, E384–E393 (2009).
Huffman, K.M. et al. Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women. Diabetes Care 32, 1678–1683 (2009).
Lewis, G.D., Asnani, A. & Gerszten, R.E. Application of metabolomics to cardiovascular biomarker and pathway discovery. J. Am. Coll. Cardiol. 52, 117–123 (2008).
Felig, P., Marliss, E. & Cahill, G.F. Jr. Plasma amino acid levels and insulin secretion in obesity. N. Engl. J. Med. 281, 811–816 (1969).
Patti, M.E., Brambilla, E., Luzi, L., Landaker, E.J. & Kahn, C.R. Bidirectional modulation of insulin action by amino acids. J. Clin. Invest. 101, 1519–1529 (1998).
Krebs, M. et al. Mechanism of amino acid–induced skeletal muscle insulin resistance in humans. Diabetes 51, 599–605 (2002).
Zhang, Y. et al. Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes 56, 1647–1654 (2007).
Floyd, J.C. Jr. Fajans, S.S., Conn, J.W., Knopf, R.F. & Rull, J. Stimulation of insulin secretion by amino acids. J. Clin. Invest. 45, 1487–1502 (1966).
Nilsson, M., Holst, J.J. & Bjorck, I.M. Metabolic effects of amino acid mixtures and whey protein in healthy subjects: studies using glucose-equivalent drinks. Am. J. Clin. Nutr. 85, 996–1004 (2007).
van Loon, L.J., Saris, W.H., Verhagen, H. & Wagenmakers, A.J. Plasma insulin responses after ingestion of different amino acid or protein mixtures with carbohydrate. Am. J. Clin. Nutr. 72, 96–105 (2000).
Meigs, J.B. et al. Genotype score in addition to common risk factors for prediction of type 2 diabetes. N. Engl. J. Med. 359, 2208–2219 (2008).
Lyssenko, V. et al. Clinical risk factors, DNA variants, and the development of type 2 diabetes. N. Engl. J. Med. 359, 2220–2232 (2008).
Kannel, W.B., Feinleib, M., McNamara, P.M., Garrison, R.J. & Castelli, W.P. An investigation of coronary heart disease in families: the Framingham Offspring Study. Am. J. Epidemiol. 110, 281–290 (1979).
Persson, M., Hedblad, B., Nelson, J.J. & Berglund, G. Elevated Lp-PLA2 levels add prognostic information to the metabolic syndrome on incidence of cardiovascular events among middle-aged nondiabetic subjects. Arterioscler. Thromb. Vasc. Biol. 27, 1411–1416 (2007).
Matthews, D.R. et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412–419 (1985).