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The rapid expansion of Type 2 Diabetes (T2D), that currently affects 90% of people suffering from diabetes, urges us to develop a better understanding of the metabolic processes involved in the disease process in order to develop better therapies. The most commonly used model for T2D research is the  db/db  (BKS.Cg-Dock7 &lt; m &gt; +/+ Lepr &lt; db &gt;/J) mouse model. Yet, a systematic  1 H NMR based metabolomics characterisation of most tissues in this animal model has not been published. Here, we provide a systematic organ-specific metabolomics analysis of this widely employed model using NMR spectroscopy.    Objectives  The aim of this study was to characterise the metabolic modulations associated with T2D in  db/db  mice in 18 relevant biological matrices.    Methods  High-resolution  1 H-NMR and 2D-NMR spectroscopy were applied to 18 biological matrices of 12  db/db  mice (WT control n = 6,  db/db  = 6) aged 22 weeks, when diabetes is fully established.    Results  61 metabolites associated with T2D were identified. Kidney, spleen, eye and plasma were the biological matrices carrying the largest metabolomics modulations observed in established T2D, based on the total number of metabolites that showed a statistical difference between the diabetic and control group in each tissue (16 in each case) and the strength of the O-PLS DA model for each tissue. Glucose and glutamate were the most commonly associated metabolites found significantly increased in nine biological matrices. Investigated sections where no increase of glucose was associated with T2D include all intestinal segments (i.e. duodenum, jejunum, ileum and colon). Microbial co-metabolites such as acetate and butyrate, used as carbon sources by the host, were identified in excess in the colonic tissues of diabetic individuals.    Conclusions  The metabolic biomarkers identified using  1 H NMR-based metabolomics will represent a useful resource to explore metabolic pathways involved in T2D in the  db/db  mouse model.    Electronic supplementary material  The online version of this article (10.1007/s11306-019-1548-8) contains supplementary material, which is available to authorized users.

NMR metabolomics identifies over 60 biomarkers associated with Type II Diabetes impairment in db/db mice