Research Summary: We induced male mice to develop type 1 diabetes mellitus (T1DM) and analyzed the abundant and aqueous metabolites from their serum using NMR spectroscopy. The early and late molecular changes that occur during the progression of the disease were identified. A diagnostic metabolic fingerprint (DMF) has been proposed that can be further assessed for its use in early diagnosis and therapeutic intervention in independent human cohorts.
Author interview
Soumya Swastik Sahoo has completed his bachelor’s and master’s degrees in Chemistry from Visva Bharati University and is currently pursuing a PhD in Chemistry at IISER Pune under the mentorship of Dr. Jeetender Chugh. His research focuses on the use of NMR-based metabolomics to identify key perturbations that lead to the establishment of metabolic disorders, including diabetes mellitus and obesity. Outside the lab, he enjoys watching true crime documentaries, is a Formula 1 fan, and finds cooking to be a therapeutic hobby.
Lab: Dr. Jeetender Chugh, Indian Institute of Science Education and Research, Pune
Lab website https://sites.google.com/acads.iiserpune.ac.in/cjeet/home
Twitter: https://x.com/jeetchem
What was the core problem you aimed to solve with this research?
The core problem addressed in this research has been the lack of specific biomarkers that can be used for early and quicker diagnosis/prognosis of T1DM. The current diagnostic methods for T1DM mainly rely on the blood tests (a series of autoantibody tests) that detect the onset of hyperglycemia, a symptom that appears only after significant pancreatic β-cell loss has occurred, thereby limiting early intervention. To bridge this gap, this study was designed to identify and visualize the specific metabolic perturbations that occur in serum—beyond glucose levels—using NMR spectroscopy, that can particularly enable the differentiation between early and established stages of T1DM. The goal was to improve diagnosis, prognosis, and risk prediction, thereby enhancing patient outcomes by providing a deeper understanding of the pathophysiology and progression of T1DM.
How did you go about solving this problem?
To address the fundamental challenge of identifying specific metabolic changes that can distinguish the early and the established stages of T1DM development, the following methodology was adopted:
- Using the streptozotocin (STZ)-induced mouse model, T1DM progression and development was followed by collecting the serum samples from these animals at various disease stages. The establishment of T1DM in mice was confirmed by a series of biochemical tests.
- Applied high-resolution 1H NMR spectroscopy to detect and quantify a broad spectrum of abundant and aqueous metabolites from the serum samples.
- Identified and quantified 50 key serum metabolites using NMR, generating detailed metabolic profiles for each stage.
- Analyzed the data with advanced multivariate statistical methods to highlight significant metabolic perturbations associated with early and late disease events, allowing visualization and comparison of molecular changes that occur as the disease progresses.
This approach enabled us to systematically identify disease-specific metabolic alterations in the form of the DMF, that we propose to be used as potential biomarkers, thereby facilitating early diagnosis, and monitoring of T1DM progression.
How would you explain your research outcomes (Key findings) to the non-scientific community?
Our body is like a complex machine that relies on hundreds of chemical signals to run smoothly. Insulin is one of these signals that is produced by the pancreatic beta-cells and plays a key role in regulating the glucose metabolism. In T1DM, our body’s defence mechanisms go against itself and thus the immune system mistakenly attacks the insulin-producing cells and kills them. However, this damage happens silently, much like a machine breaking down from the inside before showing warning signs, if any. Also, because T1DM mostly affects children, it becomes challenging to detect these warning signs. Therefore, to address these concerns, this study was designed where T1DM was developed in mice and NMR spectroscopy (a technology similar to MRI used to image human body parts, but used for small molecules) was used to identify subtle chemical changes in the blood that occur before and after T1DM becomes clinically apparent. Serum samples were collected from these mice at different stages of the disease. We identified 50 metabolites, which act as molecular messengers reflecting the body’s metabolic state, enabling us to track and understand changes associated with the onset and progression of diabetes.
We found that:
- Some metabolites change early, before clear symptoms appear, serving as potential predictors of the disease, while others emerge later, during advanced stages, and can therefore be used to track disease severity.
- These patterns give us clues to better diagnose, and monitor T1DM, possibly even before major damage happens in the body.
In short, we discovered chemical “early warning signs” and “progress trackers” for Type 1 Diabetes Mellitus that can lead to better care and earlier treatment.
Soumya’s hardwork and perseverance led to the development of a diagnostic tool to be able to follow the T1DM disease progression. We are now in the process of taking this study to human cohorts and then to clinical trials.
What are the potential implications of your findings for the field and society?
This research has significant implications for science and society:
- Improved Diagnosis and Monitoring: The diagnostic metabolic fingerprint comprising of five key metabolites, namely leucine, choline, lactate, lysine, and mannose, identified in this study alongside glucose, would enable earlier and more accurate detection of T1DM stages, supporting timely intervention and better outcomes.
- Advances in understanding T1DM: The results obtained offer insights into the molecular mechanisms driving T1DM progression.
- Broader Research Potential: The NMR-based metabolomics approach could be applied to other metabolic diseases and specific biomarker panels/fingerprints can be identified.
- Societal Benefits: Earlier diagnosis may lower healthcare costs, enhance quality of life, and inform public health initiatives.
We strongly feel that further validation of the DMF is needed in an independent patient cohort before it can be proposed for clinical use; however, the findings mark a promising step in T1DM research, diagnosis and management.
What was the exciting moment during your research?
We were really excited when the NMR spectroscopy data identified the DMF, in addition to glucose (an established biomarker for DM), that helped us differentiate between the early and late stages of T1DM. With the application of DMF, we could visualize and track disease progression at the molecular level, thereby opening new avenues for early and specific diagnosis, and intervention. We are now trying to follow up the results obtained from this study in an independent age- and sex-matched human cohort of T1DM patients and healthy volunteers.
Paper reference: Sahoo, S. S., Save, S. N., Madiwale, S., Sharma, S., & Chugh, J. (2025). Visualization of Early and Late Molecular Events Associated with the Development of Type 1 Diabetes Using NMR Spectroscopy. Journal of Proteome Research. https://doi.org/10.1021/acs.jproteome.5c00301
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