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  Metabolite ratios as potential biomarkers for type 2 diabetes: a DIRECT study

Molnos, S., Wahl, S., Haid, M., Eekhoff, E. M. W., Pool, R., Floegel, A., Deelen, J., Much, D., Prehn, C., Breier, M., Draisma, H. H., van Leeuwen, N., Simonis-Bik, A. M. C., Jonsson, A., Willemsen, G., Bernigau, W., Wang-Sattler, R., Suhre, K., Peters, A., Thorand, B., Herder, C., Rathmann, W., Roden, M., Gieger, C., Kramer, M. H. H., van Heemst, D., Pedersen, H. K., Gudmundsdottir, V., Schulze, M. B., Pischon, T., de Geus, E. J. C., Boeing, H., Boomsma, D. I., Ziegler, A. G., Slagboom, P. E., Hummel, S., Beekman, M., Grallert, H., Brunak, S., McCarthy, M. I., Gupta, R., Pearson, E. R., Adamski, J., & t Hart, L. M. (2017). Metabolite ratios as potential biomarkers for type 2 diabetes: a DIRECT study. Diabetologia, 61(1), 117-129. doi:10.1007/s00125-017-4436-7.

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アイテムのパーマリンク: https://hdl.handle.net/21.11116/0000-000B-44AC-7 版のパーマリンク: https://hdl.handle.net/21.11116/0000-000C-085E-3
資料種別: 学術論文

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URL:
https://www.ncbi.nlm.nih.gov/pubmed/28936587 (全文テキスト（全般）)
説明:
-
OA-Status:
Not specified

作成者

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 作成者:
Molnos, S., 著者
Wahl, S., 著者
Haid, M., 著者
Eekhoff, E. M. W., 著者
Pool, R., 著者
Floegel, A., 著者
Deelen, J.1, 著者           
Much, D., 著者
Prehn, C., 著者
Breier, M., 著者
Draisma, H. H., 著者
van Leeuwen, N., 著者
Simonis-Bik, A. M. C., 著者
Jonsson, A., 著者
Willemsen, G., 著者
Bernigau, W., 著者
Wang-Sattler, R., 著者
Suhre, K., 著者
Peters, A., 著者
Thorand, B., 著者
Herder, C., 著者Rathmann, W., 著者Roden, M., 著者Gieger, C., 著者Kramer, M. H. H., 著者van Heemst, D., 著者Pedersen, H. K., 著者Gudmundsdottir, V., 著者Schulze, M. B., 著者Pischon, T., 著者de Geus, E. J. C., 著者Boeing, H., 著者Boomsma, D. I., 著者Ziegler, A. G., 著者Slagboom, P. E., 著者           Hummel, S., 著者Beekman, M., 著者Grallert, H., 著者Brunak, S., 著者McCarthy, M. I., 著者Gupta, R., 著者Pearson, E. R., 著者Adamski, J., 著者t Hart, L. M., 著者 全て表示
所属:
1Deelen – Genetics and Biomarkers of Human Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394006              

内容説明

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キーワード: Arginine/metabolism Biomarkers/*blood/*metabolism Blood Glucose/metabolism Diabetes Mellitus, Type 2/*blood/*metabolism Female Glucagon-Like Peptide 1/metabolism Glucose/metabolism Glucose Tolerance Test Humans Insulin/metabolism Male Risk Factors Epidemiology Insulin secretion Metabolomics Prediction of diabetes Type 2 diabetes
 要旨: AIMS/HYPOTHESIS: Circulating metabolites have been shown to reflect metabolic changes during the development of type 2 diabetes. In this study we examined the association of metabolite levels and pairwise metabolite ratios with insulin responses after glucose, glucagon-like peptide-1 (GLP-1) and arginine stimulation. We then investigated if the identified metabolite ratios were associated with measures of OGTT-derived beta cell function and with prevalent and incident type 2 diabetes. METHODS: We measured the levels of 188 metabolites in plasma samples from 130 healthy members of twin families (from the Netherlands Twin Register) at five time points during a modified 3 h hyperglycaemic clamp with glucose, GLP-1 and arginine stimulation. We validated our results in cohorts with OGTT data (n = 340) and epidemiological case-control studies of prevalent (n = 4925) and incident (n = 4277) diabetes. The data were analysed using regression models with adjustment for potential confounders. RESULTS: There were dynamic changes in metabolite levels in response to the different secretagogues. Furthermore, several fasting pairwise metabolite ratios were associated with one or multiple clamp-derived measures of insulin secretion (all p < 9.2 x 10(-7)). These associations were significantly stronger compared with the individual metabolite components. One of the ratios, valine to phosphatidylcholine acyl-alkyl C32:2 (PC ae C32:2), in addition showed a directionally consistent positive association with OGTT-derived measures of insulin secretion and resistance (p </= 5.4 x 10(-3)) and prevalent type 2 diabetes (ORVal_PC ae C32:2 2.64 [beta 0.97 +/- 0.09], p = 1.0 x 10(-27)). Furthermore, Val_PC ae C32:2 predicted incident diabetes independent of established risk factors in two epidemiological cohort studies (HRVal_PC ae C32:2 1.57 [beta 0.45 +/- 0.06]; p = 1.3 x 10(-15)), leading to modest improvements in the receiver operating characteristics when added to a model containing a set of established risk factors in both cohorts (increases from 0.780 to 0.801 and from 0.862 to 0.865 respectively, when added to the model containing traditional risk factors + glucose). CONCLUSIONS/INTERPRETATION: In this study we have shown that the Val_PC ae C32:2 metabolite ratio is associated with an increased risk of type 2 diabetes and measures of insulin secretion and resistance. The observed effects were stronger than that of the individual metabolites and independent of known risk factors.

資料詳細

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言語:
 日付: 2018-012017-09-25
 出版の状態: 出版
 ページ: -
 出版情報: -
 目次: -
 査読: -
 識別子（DOI, ISBNなど）: その他: 28936587
DOI: 10.1007/s00125-017-4436-7
ISSN: 1432-0428 (Electronic)0012-186X (Linking)
 学位: -

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出版物 1

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出版物名: Diabetologia
種別: 学術雑誌
 著者・編者:
所属:
出版社, 出版地: -
ページ: - 巻号: 61 (1) 通巻号: - 開始・終了ページ: 117 - 129 識別子（ISBN, ISSN, DOIなど）: -